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Rankin, Jonathan. "Exploring the Effect of Maternal Physical Activity and Placental Region on Mitochondrial Protein Content and Function in the Placenta." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39339.
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The placenta is responsible for mediating fetal growth and development, thereby influencing health across the lifespan. Physical activity (PA) confers benefits to mother and baby during pregnancy, but little is known about its impact on the placenta. There were two purposes of this study: i) to determine if maternal PA during pregnancy influences placenta mitochondrial protein content and function, and ii) to determine if there were differences in placenta mitochondrial protein content and function in different regions of the placenta, namely proximal or distal to the centre of the placenta. Healthy women between 12-28 weeks gestation were recruited, and free-living PA was objectively assessed at multiple time points during pregnancy using an accelerometer. Participants were grouped by minutes of moderate-to-vigorous PA (MVPA) per day. Placenta tissue samples were collected from central and distal placental regions immediately post-birth and were used for two separate analyses. Half of the samples were flash frozen in liquid nitrogen and used for western blot analysis of mitochondrial complex I-V proteins. Fresh mitochondria were isolated from the other half of the samples, and high-resolution respirometry was used to measure placental mitochondrial respiration. There were significant positive correlations between maternal PA and mitochondrial protein content in peripheral tissue samples, but protein content was significantly higher in central tissue compared to peripheral tissue samples. In addition, state 3 respiration was higher in central tissue samples of placentas from participants with high MVPA compared to participants with low MVPA. Finally, complex I protein was higher in central tissue samples of placentas from female offspring compared to placentas of male offspring. However, many of these results are underpowered and further study is warranted. This study provides new avenues to explore the relationship between PA and placenta mitochondria in healthy populations.
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Chaudhry, Shazia Hira. "The Association of Homocysteine with Placenta-Mediated Pregnancy Complications." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39425.
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Background: Preeclampsia, small for gestational age (SGA), placental abruption, and fetal death are pregnancy complications linked to the utero-placental vasculature with serious consequences for maternal and infant well-being. Elevated homocysteine, a marker of cardiovascular disease risk, is postulated to play a role in placenta-mediated complications, but epidemiologic studies have reported inconsistent findings. The two primary objectives of this thesis were to 1: comprehensively investigate the association of homocysteine with placenta-mediated complications and examine modifying effects of pre-specified factors on this association, and 2: comprehensively investigate determinants of maternal homocysteine during pregnancy.
Methods: A systematic review and meta-analysis of prospective studies was conducted to address thesis objective 1. The Ottawa and Kingston (OaK) Birth Cohort, a prospective cohort study that recruited pregnant women between 2002 and 2009, was used to address thesis objectives 1 and 2. Homocysteine concentration was measured between 12 and 20 weeks gestation. Analyses based on the OaK Birth Cohort consisted of multivariable regressions using restricted cubic splines to model associations with continuously distributed variables.
Results: Objective 1: In an analysis of 7587 participants, a significant association between homocysteine concentration and a composite outcome of any placenta-mediated complication was observed (odds ratio (OR) for a 5 µmol/L increase: 1.63, 95% Confidence Interval (CI) 1.23-2.16) and SGA (OR 1.76, 95% CI 1.25-2.46), with potential modifying effects of the methylene tetrahydrofolate reductase (MTHFR) 677C>T variant (SGA) and high-risk pregnancy (preeclampsia).
In the systematic review identifying 30 prospective cohort or nested case-control studies, a random effects meta-analysis of pooled mean differences in homocysteine between cases and controls in 28 studies revealed significantly higher means for SGA: 0.35 µmol/L (95% CI 0.19 to 0.51, I2=33%); and preeclampsia: 0.87 µmol/L (95% CI 0.52 to 1.21, I2=92%). Significant sources of heterogeneity were study region (SGA and preeclampsia), adjusting for covariates (preeclampsia), folate status (preeclampsia), and severity (preeclampsia).
Objective 2: In 7587 OaK participants, factors related to favourable health status were associated with lower maternal homocysteine concentrations. Folic acid supplementation during pregnancy of >1 mg/day did not substantially increase serum folate concentration.
Conclusion: This thesis suggests an independent effect of slightly higher homocysteine concentration in the early to mid-second trimester on the risk of any placenta-mediated complication, SGA, and preeclampsia. Modifying effects explain some of the variability in previous studies. Favourable preconception health status was associated with lower maternal homocysteine.
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Albers, Renee Elizabeth. "Glycolytic Metabolism and Pregnancy Parameters in the Murine Placenta." Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1513781057460423.
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Von, Dadelszen Peter. "Activation of maternal leukocytes in pre-eclampsia." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341959.
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Vailes, McCauley T. "Post-Transfer Outcomes in Cultured Bovine Embryos Supplemented with Epidermal Growth Factor, Fibroblast Growth Factor 2, and Insulin-Like Growth Factor 1." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/86273.
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The high incidence of pregnancy loss is a major issue facing the cattle industry. Use of in vitro fertilized (IVF) bovine embryos has become increasingly popular to help alleviate several of these reproductive issues and provide a means to enhance genetic gain for production traits. An uterine paracrine factor cocktail containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 (IGF1) (collectively termed EFI) was recently identified as a means for improving in vitro derived bovine embryo development and trophectoderm cell numbers. The objectives of this work were to determine if EFI treatment during in vitro bovine embryo culture improves transferable embryo quality and post-transfer placental and fetal development. For each replicate (3 total), slaughterhouse-derived bovine oocytes were matured and fertilized in vitro. At day 4 post-fertilization, ≥8 cell embryos were harvested, pooled, and exposed to either the EFI treatment (10ng/ml EGF, 10ng/ml FGF2, 50ng/ml IGF1) or carrier only (1% Bovine Serum Albumin). At day 7, individual embryos were transferred to estrous synchronized beef cattle. Artificial insemination (AI) was completed on a subset of cows. The EFI treatment increased (P<0.05) the percentage of transferable embryos. Pregnancy rate at day 28 post-estrus was similar among treatments. Circulating concentrations of pregnancy-associated glycoproteins (PAGs) were determined from plasma harvested at day 28, 42 and 56. Transrectal ultrasonography was used to measure fetal crown-rump length (CRL) at day 42 and 56 and to determine fetal sex at day 60. There were no main effect differences observed across days for PAG concentration. Fetus sex by ET/AI group interactions were absent at day 28 but existed at days 42 and 56 (P<0.05). At both days, this interaction reflected fetus sex-dependent changes within the ET control group, where PAG concentrations were greater (P<0.05) in male fetuses than female fetuses. No CRL differences or interactions existed among fetal sex and pregnancy group. In summary, addition of the EFI cocktail during bovine embryo culture improved the quality of transferable embryos, but did not affect placental function or embryonic/fetal development. Increasing the numbers of transferable embryos is of value given the cost of in vitro embryo production, but no apparent increases in embryo or placental competency were detected. The EFI treatment increased (P<0.05) the percentage of transferable embryos.Master of Science
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Ajne, Gunilla. "Endothelin and the regulation of peripheral and uteroplacental vascular tone during pregnancy /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-144-X/.
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Braga, Neto Antônio Rodrigues [UNESP]. "Influência do índice apoptótico e da imuno-expressão da survivina no prognóstico de pacientes com mola hidatiforme completa." Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/106370.
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Avaliar a influência do índice apoptótico e da imuno-expressão da survivina em tecido molar no prognóstico e tratamento de pacientes com mola hidatiforme completa (MHC). Estudo observacional, retrospectivo, incluindo 78 pacientes com MHC diagnosticadas, tratadas e acompanhadas no Centro de Doenças Trofoblásticas de Botucatu/SP, Brasil, entre 1995 e 2006. Baseado nas curvas de regressão da gonadotrofina coriônica, as pacientes foram divididas em dois grupos: remissão espontânea (MHC-RE - 59 pacientes) e evolução para NTG pós-molar (MHC-NTG - 19 pacientes). Avaliação imunohistoquímica do trofoblasto viloso foi realizada pela técnica da avidina-biotina-peroxidase, usando dois marcadores: anticorpo policlonal anti-caspase-3 (diluição 1:200; Cell Signaling Technology; TX, USA) e anticorpo monoclonal anti-survivina (clone 5E8; diluição 1:100; Neomarkers, TX, USA). O índice apoptótico foi expresso em porcentual (número de células caspase-3 positivas / número de células contadas x 100). A imuno-expressão da survivina foi determinada por um método semi-quantitativo. Foi significativo o efeito do índice apoptótico sobre a evolução de pacientes com MHC, de tal modo que, o aumento de 1 unidade no índice apoptótico reduziu, em média, 61% a chance de desenvolvimento de NTG pósmolar (OR = 0,61, 95% IC: 0,45-0,84). Nenhuma influência significativa da imunoexpressão da survivina foi observada no desenvolvimento de NTG pós-molar (p > 0,01; teste exato de Fisher). Não foi possível estabelecer correlações entre efeito do índice apoptótico e da imuno-expressão da survivina e variáveis do tratamento. Nesse estudo, o índice apoptótico foi bom preditor do desenvolvimento de NTG depois de MHC, com potencial para ser usado como biomarcador prognóstico dessa doença. Ao contrário, a imuno-expressão...
To assess the influence of the apoptotic index and survivin expression of molar tissue on the prognosis and treatment of patients with complete hydatidiform mole (CHM). This retrospective observational study included 78 patients with CHM, who were diagnosed, treated and followed up in the Center of Trophoblastic Diseases, Botucatu/SP, Brazil, between 1995 and 2006. Based on chorionic gonadotrophin regression curves, patients were divided into two groups: spontaneous remission (CHM-RE - 59 patients) and post-molar GTN (CHM-NTG - 19 patients). Immunohistochemical analysis of the villous trophoblast was perfomed by avidin-biotin-peroxidase, using anti-caspase-3 polyclonal antibodies (1:200; Cell Signaling Technology; TX, USA) and anti-survivin monoclonal antibodies (clone 5E8; 1:100; Neomarkers, TX, USA). The apoptotic index was expressed in percent (number of caspase-3-positive cells / number of cells counted x 100). Survivin immuno-expression was determined by a semiquantitative method. The influence of the apoptotic index on the prognosis of patients with CHM was significant. A 1-unit increase in the apoptotic index represented an average 61% reduction in the chance of developing post-molar GTN (OR = 0.61, 95% CI: 0.45-0.84). No significant influence of survivin immuno-expression was observed on the development of post-molar GTN (p > 0.01; Fisher’s exact test). No correlations of treatment variables with apoptotic index or survivin immunoexpression were found. In this study, the apoptotic index was a good predictor of GTN development after CHM and may be a useful prognostic biomarker of this disease. On the other hand, survivin immuno-expression in the villous trophoblast had no influence on the development of post-molar GTN.
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Ambrósio, Carlos Eduardo. "A barreira placentária em cães (Canis familiaris, Linnaeus, 1758): fluxo sanguíneo materno-fetal." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21012005-111150/.
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Este estudo define a inter-relação microvascular materno-fetal e o desenvolvimento dos hematomas placentários durante diferentes períodos gestacionais em cães SRD. Placentas de 20, 35, 45 e 55 dias da prenhez foram perfundidas e fixadas para a investigação histológica e confecção de moldes vasculares, injetados com Mercox, e submetidos a corrosão para análise ao microscópio eletrônico de varredura. Os componentes fetais da placenta endoteliocorial e zonária anular do cão são irrigadas por dois ramos arteriais do cordão umbilical, um endereçado à cinta placentária, e outro ao hematoma marginal. Da artéria principal central, originam-se colaterais destinados às lamelas e vilos do labirinto no sentido feto-uterino. O desenvolvimento lamelar mostrou-se progressivo com o avançar da prenhez. Os complexos capilares na periferia dos vilos têm a forma de tufos de pêlos, cujos capilares são contínuos com o sistema venoso. Da artéria hematomal organizam-se os lóbulos microvasculares circulares, que aparecem no septo ou barreiras entre o hematoma marginal e o labirinto. Os capilares placentários maternos dispõem-se de maneira a cruzar os capilares fetais. Conseqüentemente, o fluxo sangüíneo placentário de cães Sem Raça Definida é caracterizado por um tipo de sentido único de corrente cruzada simples. O desenvolvimento dos hematomas marginais foi quantificado por morfometria. Os primeiros traços dos hematomas apareceram entre o 18º a 20º dia da prenhez como áreas hemorrágicas, delimitadas por sincíciotrofoblasto e pelo tecido septal materno. Sua justaposição à artéria materna principal, confirma a origem de sangue extravasado como oriundo dos capilares endometriais. Entre 30 a 45 dias de prenhez, os hematomas são orientados no sentido alanto-uterino, alcançando a região das glândulas endometriais, caracterizando canais de sangue extravasado, organizados em hematomas marginais ou bolsas laterais à cinta placentária central. Mediante análise estatística (KS-400 Zeiss®) correlacionamos a área dos hematomas e da cintura placentária, utilizado o teste de Pearson, o que nos revelou que os hematomas crescem até 46º dia da gestação. Do 46º dia até o parto, o tamanho da cintura ultrapassou o desenvolvimento dos hematomas, sinalizando que a fonte de nutrição do feto de cães no terço final de gestação, depende da troca transplacentária, mesmo considerada a atividade fagocitária exercida pelos hematomas.That study defines the maternal-fetal microvascular interrelationship and the placental hematomes development during different pregnant periods in the mongrel dog placenta. Placentae from 20, 35, 45 and 55 days of pregnancy were perfusion-fixed for histological investigation and vascular corrosion casts were prepared for scanning electron microscopy. Two main umbilical cord arterial branches irrigate the fetal components of annular zonary endotheliochorial dog placentae, one tributary to the centre of the girdle and the other one to the marginal hematome. From the central main artery many stem arteries arise and move through the lamellae or villi of the labyrinth in feto-maternal directions. The lamellar development showed increased substantially with progressing pregnancy. The capillary complexes at the periphery of the villi have the shape of hair tufts and lead into the venous drainage system. The hematomal artery supplies the circular lobules, which appear as a septum-like barrier between the marginal hematome and the labyrinth. The maternal placental capillaries, generally cross the fetal capillaries. Therefore, the placental blood flow in mongrel dogs is characterized by a one-way crosscurrent type interrelationship. Were analyzed the development of the marginal hematomes in dog placentae by morphometry. The first traces of hematomes appeared at 18-20 days of pregnancy as hemorrhagic area lines, and were delimited by syncytiotrophoblast and maternal septal tissue. Its location near the maternal stem artery confirms the endometrial capillary origin of the extravasated blood. Between 30-45 days of pregnancy, the hematomes were oriented in allantoic-uterine direction reaching the endometrial gland region, thus forming channels of extravasated blood, which were organized as marginal hematomes or lateral pockets to the placental girdle. Statistical analysis (KS-400 Zeiss®) was used to quantify the area of hematomes and placental labyrinth, and Pearson test correlation revealed that hematomes grow until 46 days of pregnancy. From day 46 until parturition, the size of the placental labyrinth increased and passed the development of the hematomes. We conclude that the supply of the dog fetus in the last third of pregnancy, depends more on transplacental exchange than on phagocytosis done by hematomes.
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Wright, Caroline. "Magnetic Resonance Imaging (MRI) biomarkers of placental structure and function in normal and growth restricted pregnancy." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/magnetic-resonance-imaging-mri-biomarkers-of-placental-structure-and-function-in-normal-and-growth-restricted-pregnancy(288b4214-b346-4a31-8bdd-1d4afaf65178).html.
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Fetal growth restriction (FGR) is a serious complication of human pregnancy where the fetus fails to reach its genetically pre-determined growth potential. It is a common condition, affecting 5 -15% of all pregnancies (Gardosi 2009) and is linked to a third of all antepartum deaths (CEMACH 2008). An ongoing problem for obstetricians is the difficulty in diagnosing and predicting FGR and those at highest risk of poor outcomes. Placental insufficiency is a major cause of FGR and specific abnormalities in placental morphology and function occur in this condition; constituting an abnormal FGR placental phenotype (Sibley, Turner et al. 2005). Magnetic Resonance Imaging (MRI) is a powerful tool that allows quantitative analysis of several indices relating to tissue structure and function and, therefore, is of potential use in identifying this phenotype. We hypothesised that a range of MR indices would be feasible in the placenta at 1.5 T, that these indices would be altered in FGR and that there would be correlations with relevant parameters of placental morphology. Ultimately, we aimed to assess whether these indices could be used in the assessment of FGR in utero.Using MRI we estimated placental volume, widths, length and depths in groups of women with normal and FGR pregnancies. We also measured placental relaxation times, T1 and T2, which relate to tissue composition and assessed parameters relating to blood flow using Intra-Voxel Incoherent Motion (IVIM) and Arterial Spin Labelling (ASL). We demonstrated an FGR placental phenotype that was reduced in volume but increased in depth, by around 10mm, with a shorter T2 relaxation time and lower values of D (the diffusion coefficient) measured by IVIM. A trend for reduced perfusion measured by ASL was observed in pregnancies with birthweights less than 10th centile (Gardosi, Chang et al. 1992). T2 and D also correlated with stereological indices of placental morphology.In conclusion, the studies in this thesis illustrate these MRI indices show great potential asbiomarkers for identifying the FGR placenta
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Chucri, Thaís Martins. "Imunofenotipagem de leucócitos da placenta bovina." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-10082010-180933/.
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Linfócitos e macrófagos são os principais tipos de leucócitos envolvidos no processo de tolerância materno-fetal. Os linfócitos são divididos em sub-populações de acordo com sua função e fenótipo, apesar de serem morfologicamente semelhantes. Seus tipos incluem os linfócitos T, linfócitos B e natural killers (NK). Macrófagos são células que derivam da migração dos monócitos sangüíneos para o tecido. Na placenta, os macrófagos desempenham um papel importante na regulação da apoptose, prejudicial para o desenvolvimento do embrião, e no processo de apresentação antigênica. Pouco se sabe sobre esses leucócitos na placenta bovina, como sua quantidade e onde estão presentes. Desta maneira, este trabalho tem por objetivo principal identificar as populações de linfócitos e macrófagos presentes na placenta bovina utilizando marcadores específicos e citometria de fluxo. Neste estudo, foram utilizados amostras de placentônios e região intercaruncular de vacas nos três diferentes trimestres da gestação (cinco animais de cada trimestre). As suspensões celulares obtidas foram incubadas com anticorpos monoclonais anti-CD3, anti-CD8, anti-(CD14), e anti-CD335 (uNK) e avaliados pela citometria de fluxo. No placentônio, no primeiro trimestre da gestação, a porcentagem média de células marcadas CD3+ foi de 2,37%, CD8+, 2,39%, CD14+, 1,16% e CD335+, 0,78%. Para a região intercaruncular, a porcentagem de células CD3+ foi 3,43%, 4,41% CD8+, CD14+ 3,91% e CD335+ 0,56%. No segundo trimestre gestacional, o placentônio apresentou 0,63% de células positivas para CD3+, 0,62% para CD8+, 0,34% para CD14+ e 0,55% para CD335+. Na região interplacentomal a porcentagem de células marcadas com CD3+ foi 1,59%, 1,25% para CD8+, 0,38% para CD14+ e 0,39% para CD335+. No terceiro trimestre gestacional, o placentônio apresentou 0,72% de células marcadas para CD3+, 0,75% para CD8+, 1,05% para CD14+ e 0,77% para CD335+. Na região interplacentomal a porcentagem de células marcadas para CD3+ foi 1,59%, 1,50% para CD8+, 0,60% para CD14+ e 0,48% para CD335+. Com base nos resultados apresentados, podemos concluir que a população de leucócitos na 11 placenta bovina é menos numerosa quando comparada às outras espécies como camundongos e humanos, provavelmente pelo tipo de placenta sinepiteliocorial que constitui uma barreira significativa para o sistema imunológico materno, diminuindo drasticamente a exposição do concepto a ele.Lymphocytes and macrophages are the main types of leukocytes involved in the maternal-fetal process of tolerance. Lymphocytes may be divided in subpopulations according to their function and phenotype, although being morphologically similar. Its types include the T lymphocyte, B lymphocyte and natural killers (NK). Macrophages are cells that derive from the migration of blood monocytes to the tissue. In the placenta, macrophages play an important role in the regulation of apoptosis which is deleterious to the development of the embryo and in the process of antigen presentation. There are very few references regarding the presence and quantity of leukocytes in the bovine placenta, therefore this project aims to identify lymphocytes and macrophages populations in the bovine placenta by using specific markers and flow cytometry. In this study placentomes and interplacentomal regions of cows in the three trimesters of pregnancy (five animals of each trimester) were used. Cells were incubated with the following monoclonal antibodies: anti-CD3, anti-CD8, anti-CD14,) and anti-CD335 (uNK) and evaluated by flow cytometry. In the first trimester of pregnancy, for the placentome, the average percentage of cells marked CD3+ was 2.37%, CD8+ 2.39%, , CD14+ 1.16% and CD335+ 0.78%. For the interplacentomal region the percentage of CD3+ was 3.43%, CD8+ 4.41%, CD14+ 3.91%, and CD335+ 0.56%. In second trimester of pregnancy, the placentome presented 0.63% of cells marked with CD3+, 0.62% of CD8+, 0.34% of CD14+ and 0.55% of CD335+. In the interplacentomal region the percentage of cells marked with CD3+ was of 1.59%, 1.25% of CD8+, 0.38% of CD14% and 0.39% of CD335+. In the third trimester of pregnancy, the placentomes had presented 0.72% of cells marked with CD3+, 0.75% of CD8+, 1.05% of CD14+ and 0.77% of CD335+. In the interplacentomal region the percentage of cells marked with CD3+ was of 1.59%, 1.50% of CD8+, 0.60% of CD14+ and 0.48% of CD335+. Based on the presented results, we can conclude that the leukocytes population in the bovine placenta is less 13 numerous than those described for other species like mouse and human, probably because it is a sinepithelial type placenta that constitutes a significant barrier to the maternal immunological system, diminishing drastically the conceptus antigen exposition to it.
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Lindow, S. W. "Utero-placental blood flow in hypertensive pregnancy and the effect of nifedipine administration." Master's thesis, University of Cape Town, 1987. http://hdl.handle.net/11427/27206.
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Nifedipine, in a 5mg sublingual acute administration, causes a significant fall in the systolic, diastolic and mean arterial pressure in a mixed group of pregnant hypertensives. A concurrent, significant rise in the pulse rate was seen. The utero-placental blood flow index, which is a measure of utero-placental blood flow, was not significantly reduced following the administration of Nifedipine or a placebo. The utero-placental blood flow index was found to be a consistent measure of utero-placental blood flow in resting patients. In the absence of serious side-effects it can be concluded that Nifedipine is a safe therapy in the acute treatment of hypertensive states in pregnancy.
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Bulmer, J. N. "Studies on the immunology of the human placenta in normal and pathological pregnancy." Thesis, University of Bristol, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354601.
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Kyrklund-Blomberg, Nina. "Smoking and pregnancy : with special reference to preterm birth and feto-placental unit /." Stockholm : Karolinska Institutet, 2006. http://diss.kib.ki.se/2006/91-7140-580-1/thesis.pdf.
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Reep, Daniel T. "Placental Eicosanoids and Sphingolipids in Preeclampsia." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5553.
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Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After analysis, it was found that severity of preeclampsia was correlated with a unique lipid profile. Pro-inflammatory hydroxyeicosatetraenoic acids and sphingolipids were elevated. Aspirin usage in patients who developed preeclampsia was found to attenuate accumulation of isoprostane oxidative stress markers and thromboxane production while preserving omega-3-fatty acid and increasing prostacyclin levels.
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Hunter, A. J. "Studies into the role of vascular endothelial growth factor in pre-eclampsia." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368545.
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Fotiadou, Parthena. "Effect of sodium butyrate on human placental trophoblast cells and cell lines." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322651.
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Drezza, Angela Luzia. "Associação entre crescimento neoplasico e gravidez : estudo do perfil hormonal e alterações placentarias em ratas prenhes potadoras do carcinossarcoma de walker 256." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314775.
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Orientador: Maria Cristina Cintra Gomes MarcondesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A gravidez gera modificações no organismo materno para a implantação do blastocisto, que são provocadas por hormônios como estradiol e progesterona. O tempo e curso de gravidez dependem da unidade materno / fetal, a placenta, que é o órgão responsável pela trocas entre mãe e feto, além de secretar vários hormônios, dentre eles prolactina, estrógenos e progesterona. Quando a gravidez encontra-se associada ao desenvolvimento tumoral, situação de intensa multiplicação celular, podem ocorrer disfunções no desenvolvimento embrionário. Os hormônios sexuais e a prolactina têm suas concentrações alteradas durante a gravidez, para que a mesma transcorra corretamente e, além disso, esses hormônios podem interagir com células do sistema imune. A ação do desenvolvimento tumoral, por sua vez, também é responsável pela elevação, ainda maior, na quantidade de citocinas presentes no organismo. Dessa forma, no presente trabalho, avaliou-se a influência do câncer na regulação dos hormônios necessários à gravidez, bem como no desenvolvimento placentário, uma vez que citocinas presentes no líquido ascítico de animais portadores do carcinossarcoma de Walker 256 afetariam o curso normal da prenhez em ratas. Este trabalho foi realizado através da análise de 3 grupos experimentais (ratas prenhes controle, portadoras de tumor ou inoculadas com liquido ascítico), em relação a aspectos de morfometria placentária, concentrações hormonais (estrógeno, progesterona e prolactina), imunohistoquímica e expressão protéica para os receptores placentários de estrógeno e progesterona, além dos processos de síntese e degradação protéica e biossíntese dos hormônios placentários. Através da análise dos animais inoculados diariamente com líquido ascítico, pudemos comprovar que os fatores presentes no liquido ascitico seriam, então, os maiores responsáveis pela alteração anormal de alguns hormônios durante a gravidez. Neste grupo, verificamos desbalanço hormonal semelhante ao observado no grupo Tumor e, além disso, quando comparado ao grupo Controle, apresentava fetos com peso reduzido, alterações morfológícas, de síntese e alterações na expressão de receptores de estrógeno e progesterona. Como os animais inoculados diariamente com líquido ascítico não eram hospedeiros tumorais e, portanto, não sofriam competição nutricional entre feto e as células tumorais, pudemos observar a ação de efeitos diretos ou indiretos dos fatores produzidos pelo tecido hospedeiro e/ou células tumorais, causando redução do número de células trofoblásticas gigantes e das camadas decidual e labirinto-trofoblastica, além de menor expressão protéica dos receptores de estrógeno e progesterona placentário, como redução do peso fetal. Portanto, concluímos que moléculas efetoras provenientes do sistema imunológico hospedeiro ou produzidas pelas células tumorais são capazes de alterar o curso normal da gravidez, trazendo prejuízos ao desenvolvimento placentário e, por conseguinte, fetal.
Abstract: Pregnancy causes several modifications in the maternal organism for the blastocistic implantation that are made by hormonal action, as oestradiol and progesterone. The pregnancy progress depends on the placenta, maternal / foetal unit, which exchanges nutrients, gas and substances between mother and foetus, and can produce a variety of hormones, like prolactin, oestrogen and progesterone. The association between pregnancy and tumoral growth, two situations that involve intense cell multiplication, can be extremely harmful for the foetus development. Sex hormones and prolactin have their concentrations modified during normal gestational progress and can also interact and modulate many physiological functions, as well as immune cells. In turn, tumour growth can raise body cytokines that may influence the hormones necessary to pregnancy and placenta development. In this work we analyzed 3 experimental groups (Control - pregnant rats without tumour, Tumour - pregnant tumour-bearing rats and Ascitic - pregnant rats inoculated with ascitic fluid daily) evaluating the placental morphometry, serum hormonal concentration (oestrogen, progesterone and prolactin), immunohistochemistry, protein expression of the placental oestrogen and progesterone receptors, and also measurements of ín vítro assays of protein synthesis and degradation and placenta's hormonal biosynthesis. Tumour group animais presented, when compared to the Control group, low foetus weight, molecular and morphological placenta alterations and abnormal pregnancy hormone variation (decrease in progesterone levels and increase in prolactin and oestrogen content). Animais of the ascitic fluid group also showed similar abnormal variation of these hormones in the pregnancy as observed in thé Tumour group, indicating that some factors contained in the ascitic fluid could be the greatest responsible for these alterations. Moreover, when compared to the Control group, the ascitic fluid group also presented low foetus weight and molecular and morphological placenta alterations. Since the ascitic fluid group was not tumour host and, therefore, have no nutritional competition between foetus and tumoral cells, the results allowed to observe the direct and/or indirect effects of the factors produced by the host tissue or tumoral cells. These effects included reduction of trophoblastic giants cells and decidual and trophoblastic layers, less placental and foetal oestrogen and progesterone receptor protein expression and reduced foetal weight. We concluded that humoral effectors from hosts immune system or produced by the tumour cells are able to cause pathological conditions and, during pregnancy, can also cause damages to the placental and foetal development.
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
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Braga, Neto Antônio Rodrigues. "Influência do índice apoptótico e da imuno-expressão da survivina no prognóstico de pacientes com mola hidatiforme completa /." Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/106370.
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Resumo: Avaliar a influência do índice apoptótico e da imuno-expressão da survivina em tecido molar no prognóstico e tratamento de pacientes com mola hidatiforme completa (MHC). Estudo observacional, retrospectivo, incluindo 78 pacientes com MHC diagnosticadas, tratadas e acompanhadas no Centro de Doenças Trofoblásticas de Botucatu/SP, Brasil, entre 1995 e 2006. Baseado nas curvas de regressão da gonadotrofina coriônica, as pacientes foram divididas em dois grupos: remissão espontânea (MHC-RE - 59 pacientes) e evolução para NTG pós-molar (MHC-NTG - 19 pacientes). Avaliação imunohistoquímica do trofoblasto viloso foi realizada pela técnica da avidina-biotina-peroxidase, usando dois marcadores: anticorpo policlonal anti-caspase-3 (diluição 1:200; Cell Signaling Technology; TX, USA) e anticorpo monoclonal anti-survivina (clone 5E8; diluição 1:100; Neomarkers, TX, USA). O índice apoptótico foi expresso em porcentual (número de células caspase-3 positivas / número de células contadas x 100). A imuno-expressão da survivina foi determinada por um método semi-quantitativo. Foi significativo o efeito do índice apoptótico sobre a evolução de pacientes com MHC, de tal modo que, o aumento de 1 unidade no índice apoptótico reduziu, em média, 61% a chance de desenvolvimento de NTG pósmolar (OR = 0,61, 95% IC: 0,45-0,84). Nenhuma influência significativa da imunoexpressão da survivina foi observada no desenvolvimento de NTG pós-molar (p > 0,01; teste exato de Fisher). Não foi possível estabelecer correlações entre efeito do índice apoptótico e da imuno-expressão da survivina e variáveis do tratamento. Nesse estudo, o índice apoptótico foi bom preditor do desenvolvimento de NTG depois de MHC, com potencial para ser usado como biomarcador prognóstico dessa doença. Ao contrário, a imuno-expressão... (resumo completo, clicar acesso eletrônico abaixo)Abstract: To assess the influence of the apoptotic index and survivin expression of molar tissue on the prognosis and treatment of patients with complete hydatidiform mole (CHM). This retrospective observational study included 78 patients with CHM, who were diagnosed, treated and followed up in the Center of Trophoblastic Diseases, Botucatu/SP, Brazil, between 1995 and 2006. Based on chorionic gonadotrophin regression curves, patients were divided into two groups: spontaneous remission (CHM-RE - 59 patients) and post-molar GTN (CHM-NTG - 19 patients). Immunohistochemical analysis of the villous trophoblast was perfomed by avidin-biotin-peroxidase, using anti-caspase-3 polyclonal antibodies (1:200; Cell Signaling Technology; TX, USA) and anti-survivin monoclonal antibodies (clone 5E8; 1:100; Neomarkers, TX, USA). The apoptotic index was expressed in percent (number of caspase-3-positive cells / number of cells counted x 100). Survivin immuno-expression was determined by a semiquantitative method. The influence of the apoptotic index on the prognosis of patients with CHM was significant. A 1-unit increase in the apoptotic index represented an average 61% reduction in the chance of developing post-molar GTN (OR = 0.61, 95% CI: 0.45-0.84). No significant influence of survivin immuno-expression was observed on the development of post-molar GTN (p > 0.01; Fisher's exact test). No correlations of treatment variables with apoptotic index or survivin immunoexpression were found. In this study, the apoptotic index was a good predictor of GTN development after CHM and may be a useful prognostic biomarker of this disease. On the other hand, survivin immuno-expression in the villous trophoblast had no influence on the development of post-molar GTN.
Orientador: Marilza Vieira da Cunha Rudge
Coorientador: Izildinha Maestá
Coorientador: Maria Aparecida Custódio Domingues
Banca: José Carlos Peraçoli
Banca: Odair Carlito Michelin
Banca: Jorge Fontes de Rezende Filho
Banca: Rafael Cortés Charry
Doutor
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Robineau-Charette, Pascale. "Function and Dysfunction of Fibrinogen-Like Protein 2 in Reproductive Success and Preeclampsia." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41999.
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Fibrinogen-like protein 2 (FGL2) is a known immunomodulator and prothrombinase, expressed by several subsets of immune cells. This thesis explores its potential role during the establishment of pregnancy, in mice, as well as in trophoblast function and in an immune-mediated subtype of preeclampsia (PE), in humans. We first noticed a marked subfertility in Fgl2 knockout (ko) and Fgl2 overexpressing (tg) colonies, where litters were fewer and smaller. To explain this, we mapped spatiotemporal patterns of FGL2 expression in the female reproductive tract and through the estrous cycle. FGL2 is expressed in the ovarian stroma and theca cell layer, peaking shortly before ovulation. Fgl2 ko and tg mice do not show a defect in natural or induced ovulation. FGL2 is expressed in secretory cells of the oviductal epithelium, and Fgl2 ko mice have reduced fertilization efficiency. Fgl2 tg pups are noticeably small, and we find that a reduced ratio of glycogen cells in the junctional zone of their placenta partly explains this. We next investigated the role of FGL2 in trophoblast function, using BeWo and HTR-8/SVneo cell lines. Inflammatory cytokines increase FGL2 expression in BeWo, and FGL2 overexpression promotes syncytialization. We show that it therefore rescues the deleterious effect of inflammation on syncytium formation. In a large cohort of PE and non-PE human placentas, FGL2 is high in a subtype with immune activation, and low in a canonical, anti-angiogenic subtype. Its expression correlates with incidence of chronic inflammatory histopathological lesions, likely driven by immune rejection gene sets. High FGL2 also associates with a high incidence of fibrin deposition in the placenta. Overall, we conclude that FGL2 is involved in several steps of maternal immune adaptation, both before and after pregnancy. Its absence and excess both contribute to mouse subfertility. In the developing and mature placenta, FGL2 is increased by inflammation in the trophoblast and immune compartment of the mature placenta, as a physiological attempt to re-establish immune equilibrium and protect the ongoing pregnancy.
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Evans, Phylip Wyn. "Detection of vascular endothelial growth in maternal serum and its significance in early pregnancy." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266377.
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Goddard, Kalanithi Lucy Emily. "Placental Localization and Perinatal Outcome." Yale University, 2008. http://ymtdl.med.yale.edu/theses/available/etd-08132007-124118/.
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This retrospective case-control study was designed to investigate the relationship between placental localization and intrauterine growth restriction (IUGR). Pregnant women with an anatomic survey from January 1, 2000, to December 31, 2005, and delivery of the pregnancy at Yale-New Haven Hospital (YNHH) were identified using clinical and billing records. Multiple gestation, fetal anomaly, and incomplete medical information were reasons for exclusion. Cases (N=69) were consecutive pregnancies with evidence of IUGR (estimated fetal weight <10th percentile for gestational age) at last follow-up ultrasound. Randomly selected controls (N=258) from the same time period had no evidence of IUGR. Maternal, ultrasound, delivery, and perinatal data were collected by retrospective medical record review, and IUGR cases and non-IUGR controls were compared using the Students t-test, Wilcoxon test, Chi-square analysis, Fishers exact test, and ANOVA. Placental location was determined from the anatomic survey record (obtained at 18.4 ± 1.2 weeks gestation in the IUGR group and 18.2 ± 1.0 weeks gestation in the control group; P=0.18). Multivariate logistic regression with adjustment for confounders was used to investigate the association between IUGR and placental localization. Consistent with known predictors of IUGR, the IUGR group had a higher proportion of black women (36.4% vs. 19.8%, P=0.03), chronic hypertension (26.0% vs. 3.5%, P<0.001), and hypertensive disorders of pregnancy (36.2% vs. 5.0%, P<0.001). Mean birth weights of IUGR and non-IUGR pregnancies differed by 2 kilograms (3244 ± 625 grams vs. 1277 ± 637 grams, P<0.001). IUGR infants were more likely to receive antenatal steroids, deliver preterm, deliver by cesarean section, and be admitted to neonatal intensive care. In both IUGR and non-IUGR pregnancies, the placenta was most commonly anterior or posterior. Unilateral placentas were three times more common in the IUGR group than in the non-IUGR group (17.4% vs. 5.0%, P=0.01). IUGR pregnancies were over four times as likely as control subjects to have unilaterally-located placentas compared to anterior placentas (OR 4.8, 95% confidence interval, 1.9-11.7). Adjusting for ethnicity, chronic hypertension, and hypertensive disorders of pregnancy did not affect this finding (OR 4.6, 95% confidence interval 1.6-13.5). In conclusion, we compared a group of 69 IUGR pregnancies to 258 non-IUGR controls and found intrauterine growth restriction to be associated with unilateral placentation.
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Cordier, Anne-Gaël. "Impact de la drépanocytose sur les fonctions et le développement placentaires Sickle cell disease pregnancy paradox: Impaired placental structure with maintained fetal growth Sickle cell disease profoundly impacts TRP metabolism pregnancy." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB052.
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La drépanocytose est la maladie héréditaire autosomique récessive la plus fréquente. Elle affecte la synthèse de l'hémoglobine suite à des mutations du gène de la chaîne de la ß-globine. La falciformation des globules rouges en situation d'hypoxie se manifeste par une anémie hémolytique chronique et une vaso-occlusion microvasculaire conduisant à des lésions d'ischémie-reperfusion et à des thromboses. Les taux sériques d'IL1ß, IL6, IL8, TNF-alpha et MCP1 sont significativement plus élevés chez ces patientes et participent à l'expression de molécules d'adhésion sur les cellules endothéliales. L'hémolyse chronique est responsable de la libération de l'hème et contribue à un état proinflammatoire et procoagulant qui provoque l'activation de l'endothélium. La grossesse est une situation à risque pour les femmes drépanocytaires en raison de la consommation accrue d'oxygène par la croissance fœtale et du contexte pro-inflammatoire qui augmente le risque de vaso-occlusion et d'hémolyse. La littérature a rapporté de nombreuses complications : prééclampsie, prématurité, retard de croissance intra-utérin et mort fœtale in utero. Très peu d'études sur la structure et les fonctions du placenta sont décrites dans la littérature. Le but de ce travail était de caractériser le développement et la fonction du placenta drépanocytaire et de rechercher une explication aux complications décrites. Dans notre cohorte de patientes drépanocytaires, nous avons constaté une dysmorphie placentaire majeure, malgré une croissance fœtale conservée. Notamment, nous avons observé un défaut d'arborisation des villosités choriales associé à une augmentation significative du ratio sFlt1 / PlGF à terme. L'analyse longitudinale des taux sériques de PlGF et de sFlt1 pendant la grossesse a confirmé cette altération de l'équilibre angiogénique. De plus, en réalisant des cultures cellulaires, nous avons constaté que les cytotrophoblastes des placentas drépanocytaires s'agrégeaient mais ne fusionnaient pas de manière efficace pour former le syncytiotrophoblaste et que la synthèse d'hCG associée était anormale. Cette morphologie anormale des placentas associée à une croissance fœtale conservée nous a amené à émettre l'hypothèse que des mécanismes compensatoires pourraient exister. L'environnement inflammatoire a été confirmé dans les sérums maternels par une augmentation significative de nombreuses cytokines. De plus, comme l'indolamine-2,3-dioxygénase (IDO1) est induite par les cytokines pro-inflammatoires et est impliquée dans la tolérance materno-fœtale, nous avons exploré la voie métabolique du tryptophane dans les placentas drépanocytaires. Comme attendu, le rapport kynurénine / tryptophane (activité IDO1) était significativement augmenté dans les sérums maternels et fœtaux. Par perfusion placentaire de tryptophane, nous avons mis en évidence une baisse du taux d'acide quinolinique dans le compartiment fœtal, expliquée par une forte diminution de l'activité placentaire de la Kynurénine 3-mono-oxygénase. L'impact sur la concentration en NAD, impliqué dans l'équilibre redox et dans de nombreuses voies métaboliques doit être évalué. L'analyse transcriptomique bioinformatique des gènes exprimés dans les cytotrophoblastes extraits des placentas drépanocytaires, a retrouvé des modifications du métabolisme lipidique : diminution de la Fatty acid transport protein 2, augmentation de la périlipine 2, associées à une diminution de la protéine MLN64 (transporteur du cholestérol mitochondrial). Ces résultats peuvent contribuer à expliquer la diminution des concentrations d'estradiol et de progestérone observées dans les sérums des patientes drépanocytaires à terme. Toutes ces données nous permettent d'avoir une meilleure connaissance de l'adaptation placentaire dans les grossesses drépanocytaires. Il est nécessaire de poursuivre les recherches pour établir un lien entre altération morphologique, dysfonctionnement placentaire et préservation de la croissance fœtaleSickle cell disease (SCD) is the most common inherited autosomal recessive disease that affects hemoglobin synthesis, because of mutations in the ß-globin chain gene inherited from each parent. Signs and symptoms of SCD usually begin in early childhood. The sickling of red blood cells in deoxygenated conditions manifest in chronic hemolytic anemia and microvascular vaso-occlusion leading to ischemia-reperfusion injury and infarction. Serum levels of IL1ß, Il6, TNF-alpha, IL8, MCP1 have been shown to be significantly elevated in SCD patients and activate the expression of adhesion molecules on endothelial cells. Chronic hemolysis is responsible for heme release, that contributes to a proinflammatory and procoagulant state and activates endothelium. Pregnancy is a significant concern for women with SCD because of the increased consumption of oxygen by fetal growth and the proinflammatory context that raise the risk of vaso-occlusion and hemolysis. Literature reported numerous complications including preeclampsia, premature birth, intrauterine growth retardation, and intrauterine fetal death. Very few studies on placental structure and functions are described in the literature. The aim of this work was to characterize SCD placental development and function and to search explanation of described pregnancies impairment. We first reported in a large cohort of SCD pregnancies, that major placental dysmorphias were observed, although growth retardation was not frequent. Notably, we observed a relative lack of arborization in chorial villosities with a significant increase of the ratio sFlt1 / PlGF leading at term. Longitudinal PlGF and sFlt1 levels during pregnancy confirmed this impairment in the angiogenic balance of SCD pregnancies. Furthermore, using cultured cells from SCD placentas, we found that cytotrophoblast cells aggregate normally but fuse inefficiently to form syncytiotrophoblast with an abnormal hCG synthesis. This abnormal placenta morphology with normal fetal growth led us to hypothesize that some compensatory mechanisms could counterpart those abnormal placentas. The inflammatory environment was confirmed by a significant increase of IL1 ß, IL6, IL8, IL10, TNF-alpha, MCP1 in maternal sera. Moreover, because Indoleamine-2,3-dioxygenase (IDO1) is induced by pro-inflammatory cytokines and is involved in feto-maternal tolerance, we explored tryptophan metabolic pathway in the placentas of pregnant women with SCD. As expected, Kynurenine/Tryptophan ratio (IDO1 activity) was significantly increased in maternal and fetal sera at term. By placental perfusion of tryptophan, we highlighted a drop in quinolinic acid fetal compartment concentration, explained by a strong decrease in Kynurenine 3-mono-oxygenase (KMO) activity. The impact on the NAD concentration, involved in redox balance and in numerous metabolic pathways have to be assessed. Finally, by bioinformatic transcriptomic analysis of cytotrophoblast gene expression, we have found modifications in lipid metabolism: a decrease in FATP2 (Fatty acid transport protein 2) and an increase in PLIN2 (perilipine 2) m RNA, associated to a decrease of MLN64 protein expression (mitochondrial cholesterol transporter). These results can contribute to explain the decrease in estradiol and progesterone concentrations observed in SCD maternal sera. All these datas allow us to have a better knowledge of placental adaptation to SCD pregnancies. Further investigation should be continued to link morphological impairment, placental dysfunction and fetal growth preservation
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Gustafsson, Lidström Charlotte. "Local Immune regulation in human pregnancy : with focus on decidual macrophages." Doctoral thesis, Linköpings universitet, Klinisk immunologi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-9985.
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During pregnancy, the woman carries a fetus partly foreign to her immune system, because of the expression of paternal antigens. Despite this, the fetus is normally tolerated and not rejected, as is often the case with organs in allogeneic transplantations. Systemic changes in maternal blood occur during pregnancy but, perhaps of greater importance, are changes in tissues locally in the uterus. The pregnant uterine endometrium, the decidua, is infiltrated by large numbers of leukocytes, mainly natural killer (NK) cells but also macrophages and T lymphocytes. Further, various cytokines are known to be secreted at the fetomaternal interface. However, the functions of these cells and the cytokine networks are not fully understood. The aim of this thesis was to investigate the local immune balance in normal human pregnancy decidua, both in the early phase of pregnancy and at parturition. First trimester decidual mononuclear cells, NK cells and macrophages were all shown to secrete IFN-γ, IL-4 and IL-10, as detected by ELISPOT. The secretion was not mirrored in blood from the same subjects. A significantly larger number of decidual macrophages secreted IL-10 than did their blood counterparts, indicating potential regulatory functions of this cell type. Further examination of early pregnancy decidual macrophages by microarray revealed 120 genes being differentially regulated at the transcriptional level in decidual compared to blood monocytes/macrophages. Several genes were associated with alternative activation/M2 polarization of macrophages, including CCL-18, CD209, IGF-1, MRC-1 and FN-1. Genes connected to immune regulation and tissue remodelling were common, in line with the potential functions for this cell type in utero. In addition, some molecules not previously connected to decidual macrophages, such as TREM-2, A2M and PGDS, were found to be upregulated, gaining new insights into the regulatory functions of decidual macrophages. Term decidual mononuclear cells spontaneously secrete IFN-γ, TNF, IL-4, IL-10, and TGF-β. No differences were seen between tissues obtained before and after the onset of labour, indicating that decidual mononuclear cells are not the main cell population responsible for plausible cytokine regulation in the process of labour induction. Placental and fetal membranes as well as cells in the maternal systemic circulation may instead contribute to a possible shift in immune balance prior to pregnancy termination. In conclusion, decidual leukocytes, including NK cells and macrophages, are potential producers of both Th1-like/pro-inflammatory and Th2-like/anti-inflammatory cytokines in early pregnancy as well as at parturition. Decidual macrophages are of a specialized phenotype with effector functions contributing to a proper invasion of the placenta and to immunological protection of the semi-allogeneic fetus. This thesis adds new knowledge on local immune balance during normal human pregnancy, however, the clinical significance of the presented data needs to be clarified.
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Alyahyaei, Zahraa. "The role of IL-33 and ST2 in early pregnancy." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:a6fd7c02-feeb-4fe5-b8e1-5713a65653b9.
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Regulation of the growth and differentiation of trophoblast cells is critical for successful embryo implantation and placentation. Cytokines are key players in these processes, as well as modulating the maternal immune response to prevent rejection of the conceptus. This thesis focused on the investigation of the cytokine interleukin (IL) - 33 and its receptor, ST2. ST2 has two isoforms, a functional cell surface receptor (ST2L) and a soluble decoy receptor (sST2). Previous work in this laboratory had shown that the human placenta expresses both IL-33 and sST2 at term. The aim of this thesis was to investigate IL-33 and ST2 in early pregnancy, the time when trophoblast is at its most active, with a view to better understanding their role. IL-33 and ST2 mRNA and protein were examined in 14 first trimester placentas from 6-12 weeks of gestation. IL-33 was localized to cells in the villous stroma, whereas ST2 was present in the syncytiotrophoblast, villous cytotrophoblast and the invasive extravillous cytotrophoblast of the cell columns. Secretion of sST2, but not IL-33, by the placenta was found. Investigation of pre-implantation embryos showed the presence of ST2, but not IL-33 protein. Decidualized endometrium was investigated as a potential source of IL-33 and sST2 at the maternal-fetal interface and, although mRNA for both was present, no protein could be found. The key finding was that sST2, rather than ST2L, was the predominant isoform in the placenta. This led us to reconsider the hypothesis that IL-33/ST2 interactions in the placenta are important for successful pregnancy and raised the possibility that they may have independent roles. Using trophoblast cell lines as a model, it was shown that sST2 binds to trophoblast cells, significantly inhibits their proliferation and stimulates their invasion in vitro. This is the first report of this novel role for sST2 in pregnancy. Thus these studies have shown that sST2 may play an important role in implantation and placentation through controlling trophoblast invasion.
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Faria, Miriam Rubio. "Expressão tecido específica do fator de inibição de migração de macrófagos (Mif) na interface materno fetal em camundongos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-25032010-145721/.
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Neste estudo caracterizamos a expressão de Mif nas células trofoblásticas (CT), placentárias e decidua (D) na gestação em camundongos.A imunolocalização foi realizada nos dias de gestação(dg) 7,5, 10,5, 13,5 e 17,5.Com cones ectoplacentários e placentas fetais (PL) realizou-se ensaios de Western blotting e qRT-PCR nos mesmos dg.D foram submetidas a qPCR.Aos 7,5 dg as CT gigantes e D apresentaram imunomarcação.Dos 10,5 ao 17,5 dg o Mif concentrou-se nas CTG e no espongiotrofoblasto.Na D, a imunomarcação foi menor que aos 7,5 dg.A expressão protéica na PL aumentou do 7,5 dg para o 10,5 dg (p=0,005) e para o 13,5 dg (p=0.03).A maior expressão gênica foi em 10,5 dg e diferente em 13,5 dg (p=0,048) e 17,5 dg (p=0,009).Na D, a maior expressão gênica foi em 7,5 dg e diferente dos 10,5 (0,012) e 13,5 (0,032) dg.O aumento da expressão de Mif na PL coincide com a organização em quatro camadas e com o início da circulação fetal.Esta distribuição temporal e tecido-específica sugere o MIF como modulador no início da placentação ou na sua adaptação ao ambiente uterinoThe goal of this study was to characterize Mif expression by trophoblast (TC),fetal placenta (FP) and decidua (D) during mouse pregnancy.Mif was immunolocalized at TC and D on gestation days (gd) 7.5, 10.5, 13.5 and 17.5.Ectoplacental cones (EC) and FP were used for Western blotting and qPCR.D were also used for qRT-PCR.On gd 7.5,DC and TC giant (TGC) showed strong reactivity.On gds 10.517.5,were concentrated in TGC and spongiotrophoblast cells. D reactivity was weaker than 7.5 gd.Protein expression at FP increased from gd 7.5 to 10.5 (p=0.005) and to 13.5 (p=0.03).Higher mRNA expression was found on gd 10.5 and was different from gds 13.5 (p=0.048) and 17.5 (p=0.009).At D on gd 7.5 was greater than those on gds 10.5 (0,012) and 13.5 (0,032).The up-regulation of Mif coincides with the stage that placenta assumes its four-layered organization and the fetal blood circulation begins,This temporal tissue-specific distribution and expression data suggests that Mif may play a modulator role in the onset of placentation or in it adaptation to the uterine environment
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Cureton, Natalie. "Development of nanocarriers for targeted drug delivery to the placenta." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/development-of-nanocarriers-for-targeted-drug-delivery-to-the-placenta(696cfc4f-0bd7-4fbe-9b23-d2b83a7fec7d).html.
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Pregnancy complications such as fetal growth restriction (FGR) are often attributed to poor uteroplacental blood flow, but the risk of systemic side-effects hinders therapeutic intervention. We have utilised novel placental-specific homing peptides to overcome this and have conjugated these to biocompatible liposomes. Peptide-conjugated liposomes were found to selectively bind to the outer syncytiotrophoblast layer of the human placenta and to the uteroplacental vasculature and labyrinth region of the mouse placenta. The novel vasodilator SE175 was selected as a nitric oxide donor with a favourable stability and release profile, to encapsulate in peptide-conjugated liposomes in an attempt to restore impaired uteroplacental blood flow in a mouse model of FGR, the endothelial nitric oxide synthase knockout mouse. Liposomes containing SE175 or PBS were prepared by lipid film hydration and targeting peptides coupled to the liposomal surface. Vehicle control, free SE175, PBS- or SE175-containing liposomes were intravenously injected on embryonic (E) days 11.5, 13.5, 15.5 and 17.5. Animals were sacrificed at E18.5 and fetal and placental weights recorded. Targeted delivery of SE175 significantly increased fetal weight compared to vehicle control but no other treatment groups, whilst significantly decreasing placental weight, indicating improved placental efficiency. Treatment was well tolerated, having no impact on litter size or resorptions. Targeted delivery of SE175, but no other treatment group, reduced a marker of lipid peroxidation in the placenta, indicating a reduction in oxidative stress. These data suggest that selective delivery of SE175 to the uteroplacental vasculature in peptide decorated liposomes may represent a novel treatment for FGR.
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Dubé, Chantal. "The Effect of Exercise-induced Myokines on Placental Health and Function." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36725.
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Background: Exercise in pregnancy is associated with optimized fetal growth; however, the implicated mechanisms remain unknown. We hypothesize that exercise-induced myokines may be acting on the placenta to optimize fetal growth across gestation.
Methodology: 1) Circulating profiles of 11 myokines were analyzed in 2nd trimester plasma of women characterized as active (N=14) or non-active (N=16) during pregnancy. 2) First trimester human placental explants (N=5) were treated with SPARC in a dose-dependent manner (0-150ng/ml). Metrics of placental health/function, including GLUT-4 expression/regulation, were assessed.
Results: 1) Active women demonstrated an elevation in circulating SPARC compared to non-active women (86±19pg/ml vs. 52±18pg/ml, p=0.0001). 2) Explants treated with SPARC at 100ng/ml demonstrated improved invasion, with improved maximum outgrowth distance (N=3; p=0.0219).
Conclusion: SPARC is a myokine that is elevated in the circulation of active pregnant women and is associated with improved placental invasion, suggesting a possible role of SPARC in placentation.
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O'Reilly, James Richard. "Effects of maternal stress and obesity on human feto-placental glucocorticoid exposure." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9540.
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Fetal exposure to excess glucocorticoids has been proposed as a key determinant of pregnancy outcome, as well as a predictor of long term health of the offspring through a phenomenon known as ‘developmental programming’. Obesity and ‘stress’ during pregnancy are two potential sources of altered fetal exposure to glucocorticoids. One in five pregnant women is obese at antenatal booking, and maternal obesity increases risk of offspring complications including higher birth weight, potentially leading to long-term programming effects on the offspring. Likewise, maternal anxiety during pregnancy has been identified as a programming factor, increasing the risk of psychopathology in the offspring. This thesis tests the hypothesis that in humans this association is mediated by altered action of glucocorticoids, by examining circulating levels of maternal glucocorticoids during pregnancy and through measurement of key genes in the placenta regulating fetal glucocorticoid exposure. Serum cortisol levels were measured at 16, 28 and 36 weeks gestation in n=173 class III obese (BMI 44.0±4.5kg/m2) and n=107 lean (BMI 22.8±1.6kg/m2) pregnant women. Serial corticosteroid binding globulin (CBG) concentrations were measured in a subset (n=39 lean, 26 obese) and free cortisol levels calculated using Coolen’s equation. CRH concentrations were measured at the same time points in obese (n=20) and lean (n=22) pregnant women Salivary cortisol was measured in samples collected at bed-time, waking and 30 minutes after waking. mRNA levels of candidate genes regulating glucocorticoids and fetal/placental growth including 11-beta hydroxysteroid dehydrogenase type 2 (11βHSD2), which inactivates cortisol, insulin-like growth factor 2 (IGF2) and glucocorticoid receptor (GR) were measured in first trimester (n=32), second trimester (n=15) and term (n=60) placental samples. DNA methylation of key regions controlling the expression of the IGF2, GR and 11βHSD2 genes was measured by pyrosequencing in first trimester and term samples. Levels of mRNAs encoding 11βHSD1, 11βHSD2, GR and MR were measured in term placentas collected from women from Helsinki, Finland in whom anxiety during pregnancy had been prospectively assessed using validated questionnaires. Term placental samples from a subset of the obese and lean women who had also completed stress questionnaires during pregnancy were used to examine replication of findings. Cortisol levels rose similarly during pregnancy in obese and lean but were significantly lower throughout pregnancy in obese women (p<0.05). The diurnal rhythm of cortisol was maintained. CBG levels also increased, though this change was lower in obese (1.21-fold (±0.9) vs 1.56-fold (±0.07), p<0.01). In obese women, lower calculated free cortisol at 16 weeks gestation was associated with higher birth weight after adjustment for other factors (r=-0.46, p<0.05). Placental mRNA encoding 11βHSD2 increased in association with increasing obesity in early pregnancy (r=0.44, p<0.01) and was highest in term placenta in obese women with macrosomic (>4000g) offspring (p<0.05). Placental transcript abundance of GR also increased in association with increasing obesity in early pregnancy (r=0.38, p<0.05), but was lowest in term placenta from obese with macrosomic offspring (p<0.05). IGF2 mRNA abundance was lower in the placentas of obese women with macrosomic offspring at term compared to both lean women and obese women with normal weight offspring (p<0.01). Methylation results are reported. Placental mRNA levels encoding 11βHSD1 (which converts inactive cortisone to active cortisol) at term was found to positively associate with maternal anxiety measured in the first trimester of pregnancy in a group of pregnant Finnish women (β=0.3, p<0.05). Findings were similar in the replication sample in lean women only (β=4.6, p<0.05). Lower circulating and bioavailable cortisol levels in early pregnancy, together with a greater placental ‘barrier’ to maternal glucocorticoids represent key mechanisms contributing to higher birth weight in offspring of obese women. Regeneration of active glucocorticoids in placenta and increasing placental sensitivity to glucocorticoids increases fetal glucocorticoid exposure and offers insight into the biological mechanisms underlying adverse offspring effects of maternal prenatal anxiety.
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Paula, Carla Fagundes Silva de. "Mensuração do volume e quantificação dos índices vasculares placentários pela ultra-sonografia tridimensional com power Doppler em gestações normais." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-29012009-164440/.
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Objetivo: Confeccionar curvas de normalidade do volume e dos índices de vascularização placentária segundo a idade gestacional (IG) e o peso fetal estimado (PFE). Métodos: Durante o período compreendido entre março e novembro de 2007 foi realizado estudo observacional transversal envolvendo 280 gestantes com idades gestacionais compreendidas entre 12 a 38 semanas. As gestantes foram submetidas à ultra-sonografia para avaliação do volume placentário tridimensional calculado pelo método VOCAL com quantificação da vascularização placentária por meio dos índices vasculares: índice de vascularização (IV), índice de vascularização e fluxo (IVF) e índice de fluxo (IF), usando-se o power Doppler. Os critérios de inclusão foram gestações únicas com idade gestacional confirmada à ultra-sonografia, sem doenças maternas e/ou malformações fetais. Foram derivadas equações matemáticas para as curvas do volume placentário e dos índices vasculares (IF, IV e IFV) por meio de modelo de regressão linear, assim como os percentis 10, 50 e 90 para volume placentário em relação à idade gestacional e o peso fetal estimado. Resultados: Foram incluídas no estudo 280 gestantes, das quais 14 (5%) foram excluídas por apresentarem intercorrências maternas, abortamento tardio e impossibilidade de obtenção dos dados no pósparto. Houve correlação significativa do volume placentário com a idade gestacional (r =0,572; p<0,001) e com o peso fetal estimado (r=0,505; p<0,001). O volume placentário médio variou de 83,0 cm3 para 12 semanas a 403,1 cm3 para 38 semanas. Os índices vasculares placentários não se correlacionaram com a idade gestacional, mantendo-se constante seus valores (IV vs. IG r=0,03, p=0,61; IF vs. IG r=0,03, p=0,58; VFI vs. IG r=0,06, p=0,27). Conclusão: Foram confeccionadas curvas de volume placentário segundo a idade gestacional e o peso fetal estimado, obtendo-se valores de referência. Diferentemente dos relatos prévios, os presentes resultados mostraram distribuição constante dos índices de vascularização em diferentes idades gestacionais.Objectives: The purpose of this study was to construct normograms of placental volume and placental vascular indices in normal gestations according to gestational age and fetal weight by three dimensional ultrasound power Doppler. Methods: A study was performed with 280 normal pregnant women presenting 12 to 38 weeks of pregnancy, during the period between March and November 2007. Study patients were submitted to ultrasound examination and placental volume was obtained through VOCAL method. Placental perfusion was evaluated through three-dimensional power Doppler indices: (VI) vascularization index, (FI) flow index and (VFI) vascularization and flow index. The inclusion criteria were singleton pregnancies without known clinical complications or fetal abnormalities. Equations and regression coefficients for placental volume and vascular indices were calculated according to gestational age and fetal weight. The 10th, 50th, and 90th percentiles of volumes by gestational age and estimated fetal weight were calculated. Results: The sample studied consisted of 280 pregnant women, 14 (5%) of whom were excluded from the final analysis due to some presented problems, such as maternal clinical complications, late abortion or impossibility to obtain childbirth data. There was a statistically significant correlation between placental volumes, gestational age (r=0.572; p<0.001) and estimated fetal weight (r= 0.505; p< 0.001). Mean placental volume ranged from 83,0cm3 at 12 weeks to 403,1cm3 at 38. All placental vascular indices showed a constant distribution throughout gestational age. (VI vs. GA r=0, 03, p=0, 61; FI vs. GA r=0, 03, p=0, 58; VFI vs. GA r=0, 06, p=0,27). Conclusion: Normograms of placental volumes according to gestational age and estimated fetal weight were described, generating references values. Differently from previous reports, our results showed constant distributions of all 3D-power Doppler placental volumes according to gestational age.
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Colomina, Muela Jose Maria. "Prenatal one carbon metabolism-gene interactions, placenta trace element content and their effect on pregnancy outcomes." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/441746.
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El metabolisme monocarbonat i els elements traça essencials afecten al desenvolupament i resultat de l'embaràs. Es desconeixen els efectes de diversos polimorfismes del metabolisme monocarbonat (MTHFR c.665C>T, BHMT c.716G>A, SLC19A1 c.80G>A i MTRR c.66A>G) durant l'embaràs i la seva possible modulació segons l'estat en folat; i quins factors estan associats amb les concentracions d'elements traça (zinc, coure, seleni i ferro) en la placenta.
Aquests aspectes dels esmentats polimorfismes i elements traça s’han estudiat en 617 embarassos del Reus-Tarragona Birth Cohort i 218 placentes.
Amb alt estat en folat eritrocitàri a ≤12 setmanes gestacionals (SG), i en folat plasmàtic des de les 15SG, l’MTHFR c.665C>T no va haver tenir cap efecte sobre l'homocisteïna plasmàtica. Els genotips variants de BHMT c.716 tenien menor concentració de dimetilglicina des de la meitat de l'embaràs, i a principis de l'embaràs si l'estat en folat plasmàtic era alt. Homozigots variants de MTRR c.66 van tenir major concentració d'homocisteïna plasmàtica a principis de l'embaràs, però això no es veia en els tercils extrems de folat plasmàtic.
Les concentracions en placenta de zinc, coure i seleni estaven positivament correlacionades entre si, i negativament associades al pes al néixer. Les fumadores durant l'embaràs van tenir majors concentracions de coure i seleni. La ingesta d'aquests elements traça de la dieta i/o suplements no es va associar amb les seves concentracions en placenta. Les concentracions plasmàtiques de cobalamina a ≤12SG i d'homocisteïna al part es van associar negativa i positivament, respectivament, amb les de coure en la placenta.
L'al•lel normal de MTHFR c.665 del neonat i la concentració de coure en la placenta es van associar positivament amb el creixement intrauterí restringit.
Els polimorfismes i la seva modulació segons l'estat en folat, i elements traça en placenta estudiats estan associats amb canvis en el metabolisme i resultat de l'embaràs.El metabolismo monocarbonado y los elementos traza esenciales afectan al desarrollo y resultado del embarazo. Se desconocen los efectos de varios polimorfismos del metabolismo monocarbonado (MTHFR c.665C>T, BHMT c.716G>A, SLC19A1 c.80G>A y MTRR c.66A>G) en el embarazo y su posible modulación según el estado en folato; y qué factores están asociados con las concentraciones de elementos traza (zinc, cobre, selenio y hierro) en la placenta. Se estudiaron estos aspectos de dichos polimorfismos y elementos traza en 617 embarazos del Reus-Tarragona Birth Cohort y 218 placentas. Con alto estado en folato eritrocitario a ≤12 semanas gestacionales (SG), y en folato plasmático desde las 15SG no se observó el efecto de MTHFR c.665C>T en la homocisteína plasmática. Genotipos variantes de BHMT c.716 tuvieron menor concentración de dimetilglicina desde la mitad del embarazo, y esto ocurrió también a principios del embarazo si el estado en folato plasmático era alto. Homozigotos variantes de MTRR c.66 tuvieron mayor concentración de homocisteína plasmática a principios del embarazo, pero esto no ocurría en los terciles extremos de folato plasmático. Las concentraciones en placenta de zinc, cobre y selenio estaban positivamente correlacionadas entre sí, y negativamente asociadas al peso al nacer. Fumadoras durante el embarazo tuvieron mayores concentraciones de cobre y selenio. La ingesta de estos elementos traza de la dieta y/o suplementos no se asoció con sus concentraciones en placenta. Las concentraciones plasmáticas de cobalamina a ≤12SG y de homocisteína en el parto se asociaron negativa y positivamente, respectivamente, con las de cobre en la placenta. El alelo normal de MTHFR c.665 del neonato y la concentración de cobre en la placenta se asociaron positivamente con el crecimiento intrauterino restringido. Los polimorfismos y su modulación según el estado en folato, y elementos traza en placenta estudiados están asociados con cambios en el metabolismo y resultado del embarazo.
One carbon metabolism and essential trace elements affect foetal development and pregnancy outcome. The effects of several highly prevalent one carbon metabolism polymorphisms (MTHFR c.665C>T, BHMT c.716G>A, SLC19A1 c.80G>A and MTRR c.66A>G) in pregnancy and their possible modulation by folate status, and which factors are associated with the placenta trace element concentrations (zinc, copper, selenium and iron), are unknown. These aspects of the aforementioned polymorphisms and trace elements were studied in 617 pregnancies of the Reus-Tarragona Birth Cohort and 218 placentas. With high erythrocyte folate status at ≤12 gestational weeks (GW) and with high plasma folate status from 15GW on, the homocysteine-enhancing effect of MTHFR c.665C>T was not observed. Lower plasma dimethylglycine in BHMT c.716 variant genotypes was found at mid-late pregnancy, and this was also true for early pregnancy if plasma folate status was high. MTRR c.66 variant homozygotes had higher plasma homocysteine concentration at early pregnancy, and after plasma folate status stratification this was not observed in the extreme tertiles. Placenta concentrations of zinc, copper and selenium were positively correlated, and negatively associated with birth weight. Smoking during pregnancy was associated with higher copper and selenium concentrations. Intake of these trace elements from food and/or supplements was not associated with their concentrations in placenta. Plasma cobalamin at ≤12GW and homocysteine at labour were negatively and positively, respectively, associated with placenta copper concentrations. MTHFR c.665 normal allele in the neonate and placenta copper concentration were positively associated with intrauterine growth restriction. These studied polymorphisms and their modulation by folate status, and the placenta trace elements, are associated with metabolic changes and pregnancy outcome.
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Dunn-Fletcher, Caitlin E. "Expression and Function of Corticotropin-releasing Hormone in Anthropoid Primate Placenta." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543581518246546.
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SANTOS, Carlos Anselmo dos. "Alterações placentárias associadas à hipertensão arterial em éguas com laminite crônica no terço final da gestação." Universidade Federal de Pelotas, 2013. http://repositorio.ufpel.edu.br/handle/ri/2506.
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Previous issue date: 2013-01-17The cardiovascular changes in horses with laminitis are described since the 70's, however few studies have been conducted to demonstrate such changes in pregnant mares with chronic laminitis. The present study aims to evaluate blood pressure, heart rate, serum cortisol levels, gestational age and placental changes of pregnant mares with chronic laminitis and its consequences for fetal morphometry. A prospective longitudinal case-control was conducted in 6 Thoroughbred horse farms in southern Rio Grande do Sul - Brazil. Were used a total of 20 multiparous mares (10 control animals and 10 animals with chronic laminitis). The selected animals were subjected to clinical examination, blood sample collection and blood pressure measurement on alternate days in the last month of pregnancy. Serum levels of cortisol were obtained by chemiluminescence, and blood pressure measurement by indirect method and apparatus for noninvasive oscillometric sphygmomanometer at the base of the tail. Assessment of placental was effected by using the histological method of Schlafer (2004) and morphometric using ImageJ® software. Mean control group regarding measurements of systolic blood pressure were 98,3 ± 1,41 mmHg. The average diastolic blood pressure was 62,2 ± 1,14 mmHg. The mean heart rate was 44 ± 0,53 bpm and the mean serum cortisol levels were 5,06 ± 0,14 μg/dL. The group of pregnant mares with chronic laminitis kept the mean systolic blood pressure and heart rate higher than the control group, being respectively 116 ± 6,73 mmHg and 52 ± 4 bpm. The average values of diastolic blood pressure was 70 ± 7,3 mmHg and mean serum cortisol was 5,07 ± 0,19 μg/dL with no difference compared to the control group. The placentas of pregnant mares with laminitis had higher number of chronic histological changes and higher wall thickness / lumen than the control group (p <0,05). The foals born from mares of the control group had higher birth weight than foals born from chronic laminitis s group mares (p <0,05).
As alterações cardiovasculares em cavalos com laminite são descritas desde a década de 70, porem poucos estudos foram realizados para demonstrar tais alterações em éguas gestantes com laminite crônica. O presente estudo tem como objetivo avaliar a pressão arterial, frequência cardíaca, níveis de cortisol séricos, tempo gestacional e alterações placentárias de éguas gestantes com laminite crônica e suas consequências sobre a morfometria fetal. Foi realizado um estudo prospectivo longitudinal de caso controle em 6 criatórios de equinos Puro Sangue Inglês na região sul do Rio Grande do Sul Brasil. Foram utilizados um total de 20 éguas multíparas (10 animais do grupo controle e 10 animais com laminite crônica). Os animais selecionados foram submetidos ao exame clínico, coletas de sangue e mensurações da pressão arterial em dias alternados no último mês de gestação. Os níveis séricos de cortisol foram obtidos pelo método de quimiluminescência, e a aferição da pressão arterial através do método indireto e não invasivo por aparelho de esfigmomanômetro oscilométrico na base da cauda. A avaliação placentária foi efetuada por meio histológico utilizando o método de Schlafer (2004) e morfométrico utilizando o programa de domínio público ImageJ. Os valores médios do grupo controle referentes às aferições da pressão arterial sistólica foram de 98,3 ±1,41mmHg. O valor médio da pressão arterial diastólica foi de 62,2 ±1,14mmHg. A frequência cardíaca média foi de 44 ±0,53 bpm e as médias dos níveis séricos de cortisol foram de 5,06 ±0,14 μg/dL. O grupo de éguas gestantes com laminite crônica manteve as médias de pressão arterial sistólica e frequência cardíaca mais altas que ao grupo controle, sendo respectivamente, 116 ±6,73 mmHg e 52 ±4 bpm. Os valores médios obtidos da pressão arterial diastólica foi de 70 ±7,3 mmHg e a media dos níveis séricos de cortisol foi de 5,07± 0,19 μg/dL não havendo diferença em relação ao grupo controle. As placentas do grupo de éguas gestantes com laminite crônica obtiveram maior número de alterações histológicas e maior relação de espessura parede/luz arterial que o grupo controle (p<0,05). Os potros provenientes das gestações de éguas do grupo controle obtiveram peso ao nascimento superior aos potros nascidos do grupo de éguas com laminite crônica (p<0,05).
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Stenqvist, Ann-Christin. "Immunomodulation during human pregnancy : placental exosomes as vehicles of immune suppression." Doctoral thesis, Umeå universitet, Klinisk immunologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-87566.
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The mammalian pregnancy comprises a challenge to the maternal immune system since the fetus is semi-allogeneic and could thus be rejected. Pregnancy success is associated with the placenta that is not only essential for oxygen supply, nourishment and pregnancy hormones but also plays a role in the protection of the fetus against maternal immunologic attack. The aim of the current studies was to elucidate the role of human placenta as an immunomodulatory organ with a special focus on placental exosomes as vehicles for establishment of maternal tolerance to the fetus. We discovered that the syncytiotrophoblast in human normal pregnancy constitutively produces and secretes exosomes. Exosomes are 30-100 nanometer-sized membrane vesicles of endosomal origin that convey intercellular communication. Exosomes are produced and released through the endosomal compartment and reflect the type and the activation state of the cells that produce and secrete them. They carry cytosolic and membrane-bound proteins and nucleic acids and can influence and re-program recipient cells. Depending on their interactions with cells of the immune system they can be divided into immunostimulatory or immunosuppressive. We developed methods for isolation and culture of trophoblast and placental explants from human normal first trimester pregnancy and isolated exosomes from the culture supernatants. These exosomes were characterized biochemically and functionally regarding mechanisms with potential importance in the establishment of maternal tolerance towards the fetus. The following aspects were studied: 1) exosomal modulation of the NKG2D receptor-ligand system, a major cytotoxic pathway for NK- and cytotoxic T cells and thus potentially dangerous to the fetus; 2) placental exosome-mediated apoptosis of activated immune effector cells; and 3) Foxp3-expressing T regulatory cells in human pregnant uterine mucosa, the decidua. Using immuno electron microscopy we show that human early syncytiotrophoblast constitutively expresses the stress-inducible NKG2D ligands MICA/B and ULBP1-5, and the apoptosis inducing molecules FasL and TRAIL. While MICA/B were expressed both on the cell surface and intracellularly on the limiting membrane of multivesicular bodies (MVB) and on exosomes, the ULBP1-5, FasL and TRAIL were solely processed through the MVB of the endosomal compartment and secreted on exosomes. The NKG2D ligand-expressing placental exosomes were able to internalize the cognate receptor from the cell surface of activated NK- and T cells thus down regulating their cytotoxic function. In our studies of apoptosis we found that placental exosomes carry the proapoptotic ligands FasL and TRAIL in their active form as a hexameric complex of two homotrimeric molecules, required for triggering of the apoptotic signaling pathways. This finding was supported by the ability of isolated placental FasL/TRAIL expressing exosomes to induce apoptosis in activated peripheral blood mononuclear cells (PBMC) and Jurkat T cells. Additionally, we studied Foxp3-expressing T regulatory (Treg) cells in paired human decidual and blood samples from pregnant women compared to non-pregnant controls. The CD4+CD25+Foxp3+ Treg cells were 10 fold enriched in the decidual mucosa compared to peripheral blood of pregnant women and non-pregnant controls. We discovered a pool of Foxp3-expressing, CD4+CD25- cells in human decidua, a phenotype consistent with naïve/precursor Foxp3+ Treg cells. These results suggest local enrichment of Treg cells in decidua of normal pregnancy. Furthermore, we have results indicating that the exosomes, isolated from placental explant cultures, carry PD-L1 and TGFβ on their surface, molecules known to promote induction of Treg cells. Taken together, our results provide evidence that placental exosomes are immunosuppressive and underline their role in the maternal immune modulation during pregnancy. The constitutive production and secretion of immunosuppressive placental exosomes create a protective exosomal gradient in the blood surrounding the feto-placental unit. This “cloud of immunosuppressive exosomes” conveys immunologic privilege to the developing fetus and thus contributes to the solution of the immunological challenge of mammalian pregnancy.
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Viana, Laís Rosa 1988. "Avaliação do perfil de aminoácidos fetal e materno e atividade placentária em camudongas NMRI portadoras do adenocarcinoma de colon (MAC16) submetidas com dieta rica em leucina." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314497.
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Orientador: Maria Cristina Cintra Gomes MarcondesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A gravidez envolve várias etapas de ajustes fisiológicos, sendo que algumas complicações clínicas podem surgir ao longo deste processo. Dentre as complicações durante a gestação, o câncer destaca-se mais pela sua coexistência com essa complexa condição metabólica, do que pela sua incidência. Na mãe portadora de doença neoplásica, pode haver competição nutricional entre feto e tumor, resultando em alterações no crescimento e metabolismo de ambos. A manipulação da dieta e suplementação nutricional podem minimizar os danos causados pelo tumor. A leucina é um aminoácido que participa do processo de síntese protéica tecidual de forma estrutural e também atua diretamente na sinalização celular; considerando organismos portadores de câncer, a leucina age inibindo o processo de proteólise estimulando o processo de proteogênese. O objetivo desse trabalho foi avaliar o crescimento fetal em associação ao desenvolvimento de câncer em camundongas prenhes submetidas à dieta rica em leucina. Os resultados obtidos referem-se a avaliação de fêmeas adultas (60-90 dias) da linhagem NMRI, prenhes, submetidas a suplementação nutricional com leucina portadoras ou não do adenocarcinoma de colon MAC16 e inoculadas ou não com líquido ascítico ativo ou inativado . Foram avaliados, nessas fêmeas, dados morfométricos como peso relativo de coração, fígado, baço, adrenal, músculo e placenta, sendo observado discreta diminuição do peso relativo da carcaça, coração, músculo e placenta nos grupos portadores de tumor e inoculados com líquido ascítico ativo, quando comparados aos seus grupos controles. Essa diminuição, provavelmente foi induzida pelo crescimento tumoral ou por seus fatores presentes no líquido ascítico. Em contrapartida, houve aumento no peso relativo do fígado e baço nos grupos portadores de tumor, inoculados com líquido ascítico ativo bem como inativo. Também foi possível observar que, nos grupos suplementados com leucina, o peso relativo de alguns órgãos como, músculo e placenta, foi superior ao dos grupos que receberam a dieta controle, mostrando possível efeito protetor da leucina contra a espoliação desses tecidos. Foram analisados também dados bioquímicos nos soros materno e fetal, além da composição corpórea fetal. No soro materno observamos que houve diminuição discreta na concentração de albumina e glicose nos grupos portadores de tumor. Houve aumento da reabsorção de fetos por fêmea nos grupos portadores de tumor e inoculados com líquido ascítico, e ainda nesses mesmos grupos houve modulação desse efeito quando houve suplementação nutricional com leucina. No soro fetal, houve diminuição na concentração de proteínas totais, albumina e glicose, alem do aumento dos aminoácidos gliconeogênicos, como alanina e glutamina, nos grupos implantados com o tumor submetidos a dieta controle. Em contrapartida, os grupos com leucina mostraram discreto efeito protetor da suplementação com esse aminoácido. Concluímos, que os efeitos do crescimento tumoral são para alguns parâmetros mimetizados com a inoculação de líquido ascítico, porém podem ser modulados, na maioria dos parâmetros, com a suplementação nutricional de leucina. A suplementação nutricional com a leucina promoveu efeito benéfico, contribuindo para a manutenção e modulação dos efeitos deletérios causados pela presença da neoplasia, como manutenção da glicemia e proteína totais séricas, além de diminuir reabsorções fetais e também contribuiu para melhorar a atividade placentária nas mães, independente da inoculação ou não do líquido ascítico
Abstract: Pregnancy is a complex process involving several physiological steps and some clinical complications can alter the homeostasis adjustments during this process. Among the complications during pregnancy, cancer is very important for its coexistence than the incidence with this complex metabolic condition. In tumour-bearing mother, there is possible nutritional competition between foetal and tumour, resulting impaired growth and metabolic changes in both mother and foetus. The nutritional supplementation can minimize the damage caused by the tumour. Leucine acts as a cell signalling improving protein synthesis process and tissue structure. Considering cancer patients, leucine inhibits the process of proteolysis. The aim of this study was to evaluate foetal growth in association with cancer development in pregnant mice subjected to leucine-rich diet. We evaluated NMRI pregnant mice (60-90 days-old) feeding control or leucine-rich diet, bearing or not MAC16 colon adenocarcinoma and inoculated or not with active- or inactivated-ascitic fluid. Morphometric data showed decrease in the relative weight of carcass, heart, muscle and placenta in tumour-bearing groups and active-ascitic fluid injected groups. These results may be induced by tumour growth or its factors presented in ascitic fluid. In contrast, we observed increase in relative liver and spleen in tumour-bearing and both active or inactivated ascitic-fluid-inoculated groups. In groups supplemented with leucine, the muscle and placenta relative weight increased in comparison to control diet group, suggesting a possible protective effect of leucine against these tissues wasting. Biochemical data were also analyzed in maternal and foetal serum, and foetal body composition. Maternal serum showed slight decrease in serum albumin and glucose in tumour-bearing groups and also increase in gluconeogenic amino acids, such as glutamine and alanine. The foetuses resorption per female increased in all tumour-bearing groups and ascitic-fluid-inoculated dams. The foetal body water was increased in tumour-bearing animals, and also enhanced the serum pro-inflammatory cytokines and glucagon. We conclude that some effects produced by tumour growth can be similar by the ascitic fluid injection, and can be partially modulated by leucine-rich diet. Nutritional supplementation with leucine promoted beneficial effect, contributing to the maintenance and modulation of the deleterious effects caused by the presence of cancer. These effects can be related to maintenance of blood glucose and serum total protein, and reduction of fetal resorption and also improved the signalling proteins activity in placenta tissue, independent of the inoculation of the ascitic fluid
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
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Moschidou, Dafni. "A new source of stem cells in amniotic fluid and placenta in 1st trimester of pregnancy." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/5484.
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Mesenchymal stromal cells (MSC) are multipotent cells found in fetal, neonatal and adult tissues. Fetal MSC have advantageous characteristics over their adult counterparts, and the regenerative potential of fetal blood MSC has recently been shown in a model of skeletal dysplasia and renal failure. Although fetal blood MSC can be isolated during ongoing pregnancy, the clinical effectiveness of using fetal blood-derived MSC for prenatal fetal cell therapy is constrained by the invasive nature of blood sampling procedure. With amniocentesis and chorionic villus sampling (CVS), fetal MSC can be obtained with minimal invasion. The aim of this study was to characterise stem cells from 1st trimester amniotic fluid (AF) and placenta by comparing their phenotype with MSC from 1st trimester bone marrow and 2nd trimester AF. Cells from all sources have similar immunophenotype, express pluripotency markers and telomerase, but 1st trimester AF stem cells have higher kinetics. The cells can differentiate into 3 lineages (bone, fat and cartilage), form embryoid bodies (EB) in vitro and can be transfected with high efficiency using non-viral methods. The migration potential of fetal MSC was also investigated using in vitro migration assays, to recapitulate the in vivo mechanisms involved in donor cell recruitment to various tissues and delineate the pathways involved. Fetal blood MSC and AF stem cells were shown to express CXCR4, the stromal cell-derived factor-1 (SDF-1) receptor, intracellularly but not on the cell membrane and migrate to SDF-1 gradients and to osteoblast cultures derived from the Osteogenesis Imperfecta mouse (oim), but not wild type bones. Pre-stimulation with oim plasma up-regulated CXCR4 and increased chemotaxis to SDF-1 and oim bone. Conclusively, 1st trimester AF and placenta are a new source of stem cells with great potential for future cell therapy applications. Also, initial experiments indicate the importance of the SDF-1/CXCR4 axis for stem cell recruitment to the site of injury.
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Ahmed, Tasfia. "Micronutrient Intake During Pregnancy: Effects of Excessive Folic Acid on Placental Health and Function." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32167.
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Background: In addition to a diet including fortified dietary staples, the use of prenatal multivitamin supplements among women has been shown, in some cases, to lead to excessive micronutrient intake levels for nutrients such as folic acid (FA). It was therefore hypothesized that prenatal vitamin supplementation, in addition to a standard Canadian diet, would place pregnant Canadians at risk for excessive FA intake. With little available research on the potential negative impact of excess FA intake in pregnancy, it was further proposed that high concentrations of FA may adversely affect placental health and function. Thus, the aim of the current study was three-fold: 1) To determine micronutrient intake in a large Canadian cohort of pregnant women; 2) To determine the extent to which FA intake in this cohort may exceed the tolerable upper intake level (UL) after prenatal supplementation; and 3) To determine the effects of excessive FA exposure on placental health and function in vitro.
Methodology: Second trimester 3-day food records of pregnant women (N=216) were analyzed for micronutrient intake using ESHA Food ProcessorTM. Nutrient intake values were compared to established Dietary Reference Intake (DRI) values. In a series of experiments, the effects of exogenous folic acid (2-4000 ng/ml) on placental health and function were examined in two placental cell lines [HTR-8/SVneo (N=3) and BeWo (N=3)], and a human placenta explant model (N=6). Following a 48-hour incubation period, the effects of excessive folic acid exposure on placenta cell proliferation, viability, and apoptosis were determined, along with evaluation of placenta cell function via cell invasion and B-hCG hormone release assays.
Results: Through dietary sources alone, most pregnant women studied were consuming adequate levels of most micronutrients. However the majority of examined women (>50%) demonstrated a risk of dietary inadequacy for vitamin D, vitamin E, folate, and iron. In the examined cohort, 83% of study participants reported prenatal supplement usage. In vitro exposure of human placenta cells and explants to excessive FA concentrations resulted in no significant differences in cellular proliferation, apoptosis, invasion, or B-hCG hormone production. However, decreased cell viability was observed in BeWo cells at increased FA concentrations (200-2000 ng/mL).
Conclusion: Food sources alone do not appear to provide women in Canada with adequate intake of all micronutrients recommended for a healthy pregnancy. Though a prenatal supplement containing FA may be necessary for most women, current FA levels in many prenatal supplements may lead to excessive FA intake above the established UL. Yet, as measured in this study, high FA concentrations do not seem to adversely affect most primary indicators of placental cell health or function.
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Nordor, Akpéli. "Toward the identification of cancer/placenta epigenetic switches." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB097.
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Les cellules placentaires portent un génome différent du génome maternel, puisque 50% de leurs gènes proviennent du génome paternel. Cependant, comme les cellules cancéreuses après la transformation néoplasique, elles réussissent à envahir les tissus de leur hôte, échapper à son système immunitaire et induire une angiogenèse afin d’établir la grossesse. Les cellules cancéreuses et placentaires arborent aussi une différence majeure : alors que de tels mécanismes typiques des cancers sont incontrôlés dans les cellules cancéreuses, ils sont spatialement et temporairement contrôlés dans les cellules placentaires saines. Ainsi, le recherche sur le « concept cancer/placenta » – l’utilisation du placenta pour mieux comprendre le cancer – peut aboutir à l’identification de biomarqueurs et d’approches thérapeutiques innovantes en oncologie, tout comme en gynécologie-obstétrique. Par exemple, les efforts de recherche portant sur l’expression des gènes CGB, codant pour la sous-unité ß de l’hormone chorionique gonadotrope humaine, dans les cellules cancéreuses et placentaires a mené au développement d’un biomarqueur largement utilisé pour la prise en charge de multiples cancers. Il est aussi intéressant de noter que ce même biomarqueur est aussi utilisé pour le dépistage d’aneuploïdies fœtales. De même, le clonage d’INSL4, codant pour le précurseur du peptide placentaire précoce ressemblant à l’insuline (pro-EPIL), dans des cellulaires placentaires précoces, a mené au développement d’un biomarqueur faisant actuellement l’objet d’études cliniques. Avec l’émergence de l’épigénétique, des études de la méthylation de l’ADN, la caractéristique épigénétique la mieux comprise, ont montré que les loci de gènes CGB et INSL4 sont hypométhylés dans les cellules cancéreuses et placentaires ; ce qui pourrait refléter l’hypométhylation globale caractéristique de ces deux types cellulaires. Par conséquent, le projet doctoral présenté dans cette thèse a exploré les modifications des paysages épigénétiques des cellules placentaires au cours de la grossesse et des cellules cancéreuses au cours de la transformation néoplasique. Ce projet a contribué initialement au développement d’un test d’immunoanalyse qui détecte l’hCGß de type II, spécialement codée par un sous-groupe de gènes CGB et détectée dans le sérum de patients atteints de cancers non-placentaires et de trisomie 21 fœtale. Ce test d’immunoanalyse, avec un test similaire développé pour la détection de pro-EPIL, a aussi été utilisé pour des études de preuve de concept précoces quant à l’effet de la méthylation de l’ADN sur l’expression de l’hCGß de type II et de pro-EPIL dans des surnageants de culture cellulaire. En fin de compte, ce projet a mené à la première comparaison directe et pan-génomique de la méthylation de l’ADN dans des cellules cancéreuses au cours de la transformation néoplasique et dans des cellulaires placentaires au cours de la grossesse. Cette étude a porté sur des données, disponibles publiquement, générées à partir de biopsies de 13 types de tumeurs, de villosités choriales (tissus placentaires) et d’autres tissus sains. Elle a également porté sur des données originales générées par nos soins à partir d’échantillons placentaires uniques : des cellules cytotrophoblastiques isolées de villosités choriales ex vivo. Toutes les données inclus dans cette étude ont été générées sur une plateforme de puces à ADN pour la mesure de la méthylation au niveau de 485 512 sites CpG pour chaque échantillon. En combinant, des logiciels innovants reposant sur la puissance d’algorithmes de lissage statistique et sur un solide rationnel biologique, cette étude a ainsi contribué à l’identification de motifs d’hypométhylation à l’échelle du mégabase distinguant les cellules placentaires du début de la grossesse de celles de la fin de la grossesse tout comme ils distinguent les cellules cancéreuses des cellules normales. (...)Placental cells carry a genome different from the maternal genome, as 50% of it originate from the paternal genome. However, like cancer cells after neoplastic transformation, they successfully invade their host tissues, escape its immune system and induce angiogenesis in order to establish the pregnancy. Cancer and placental cells also display a major discrepancy: while such hallmarks of cancer mechanisms are uncontrolled in cancer cells, they are spatially and temporally controlled in healthy placental cells. Thus, research on the “cancer/placenta concept” – the use of the placenta to better understand cancer – can lead to innovative biomarkers and therapeutic approaches in oncology as well as in gynecology and obstetrics. For example, research efforts on the expression of the CGB genes, encoding for the human chorionic gonadotropin beta subunit (hCGß), in cancer and placental cells have led to the development of a biomarker widely used for the management of various cancers. Interestingly, this same biomarker is also used for the screening of fetal aneuploidies. Likewise, the cloning of INSL4, encoding for the precursor of the early placenta insulin-like peptide (pro-EPIL) in early pregnancy placental cells, has led to the development of a biomarker currently investigated in the clinical setting. Following the rise of epigenetic, studies on DNA methylation, the most well understood epigenetic mark, showed that the loci of CGB genes and INSL4 are hypomethylated in cancer and placental cells, which may reflect a global hypomethylation also characteristic of these cells. Therefore, the doctoral project presented in this dissertation had explored modifications in the epigenetic landscape of placental cells throughout pregnancy and cancer cells throughout neoplastic transformation. This project initially contributed to the development of an immunoassay detecting type II hCGß, specifically encoded by a subset of CGB genes and detected in the serum of patients with non-placental cancers and fetal Down Syndrome. This immunoassay, along with another one directed to pro-EPIL, was also used for an early proof of concept study regarding the effect of DNA methylation on the expression of type II hCGß and pro-EPIL in cell culture supernatants. Ultimately, this project led to the first direct genome-wide comparison of DNA methylation in cancer cells throughout neoplastic transformation and in placental cells throughout pregnancy. It included publically available data generated from biopsies of 13 types of tumors, chorionic villi (placental tissues) and other normal tissues. It also included original data generated from unique placental samples: villous cytotrophoblastic cells isolated ex vivo from chorionic villi. All datasets were generated on a microarray platform measuring DNA methylation at 485,512 CpG sites in each sample. Combining innovative software that leverages the power of statistical smoothing algorithms and a strong biological rationale, this study thus contributed to the identification of megabase-scale patterns of hypomethylation distinguishing early pregnancy from late pregnancy placenta cells as they distinguish normal from cancers cells. Strikingly, the affected genomic regions encompassed genes related to hallmarks of cancer mechanisms such as epithelial-mesenchymal transition (EMT), innate and acquired immune response, and hypoxia. Taken together, these results suggest the hypothesis that patterns of DNA methylation might contribute to “cancer/placenta epigenetic switches” allowing placental implantation and neoplastic transformation when turned “on”, while preventing the placenta to degenerate into an aggressive tumor when turned “off”
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Freitas, Murilo Rodrigues Barbosa de. "O efeito do selênio em ratas Wistar prenhas infectadas pela cepa Y de Trypanosoma cruzi." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-31102014-102620/.
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O selênio (Se) é um micronutriente importante na dieta de mamíferos e tem sido descrito com importante papel na função imune. É constituinte de mais de 25 selenoproteínas na forma do aminoácido selenocisteína, sendo este elemento crítico na manutenção do sistema de defesa antioxidante. Uma dieta complementar com Se pode ser benéfica no tratamento de doenças correlacionadas com altos níveis de estresse oxidativo, como a doença de Chagas, enfermidade negligenciada causada por Trypanosoma cruzi. O objetivo deste estudo foi avaliar os efeitos do Se em ratas Wistar prenhas infectadas pela cepa Y de T. cruzi. O tratamento com Se desencadeou aumento no peso e comprimento fetal, bem como no diâmetro e peso placentário. Também foi observada diminuição da parasitemia. Não ocorreram alterações significativas nas concentrações de NO e no número de ninhos de amastigotas no coração. A avaliação histológica das placentas mostrou elevado número de ninhos de amastigotas nos animais do grupo infectado e tratado. A redução da concentração de citocinas pró-inflamatórias e de populações de células T desencadeou uma resposta voltada ao padrão Th-2, característico da gestação, fato que provavelmente contribuiu no aumento do parasitismo placentário encontrado nos animais tratados com Se. Assim, é possível que a administração de Se, durante a prenhez, poderia alterar a resposta imune placentária local, favorecendo a instalação do parasita. Mais estudos são necessários para avaliar a interação entre o Se e a doença de Chagas durante a prenhez.The selenium (Se) is an essential micronutrient in the diet ofmammals and has an important role in the immune function. A range of 25 selenoproteinshas Sein its structure and most of them in the form of amino acid selenocysteine, being this element involved in the in maintenance of the antioxidant defense. Diet with Se is beneficial in the treatment of diseases correlated with high levels of oxidative stress, like Chagas\' disease, a neglected illness caused by Trypanosoma cruzi. The objective of this study was to evaluate the effects of selenium in the immune response of pregnant Wistar rats infected withtheY strain of T. cruzi. Se treatment triggered enhanced fetal weight and length and placental diameter and weight. It was observed decreased parasitemia. No significant alterations in NO concentrations and amastigote nests in heart were observed. The histological evaluation of placenta displayed an enhanced number of amastigote nests in infected and Se treated animals. The reduction of pro-inflammatory cytokines and T cell populations triggered a Th-2 immune response, which is the hallmark of the gestation period. This fact probably led to the raise in parasite nests in placenta of infected and Se treated animals. So it is possible that the Se supplementation during pregnancy could impair the local placental immune response. Further studies are needed to assess the interaction between selenium and the acute Chagas\' disease during pregnancy.
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Alison, Marianne. "Imagerie fonctionnelle du placenta en IRM." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112329.
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L’insuffisance placentaire par défaut de vascularisation est une pathologie fréquente de la grossesse, de diagnostic difficile, avec des complications potentiellement graves (retard de croissance intra utérin, prééclampsie). L’objectif de ce travail de Thèse a été de développer l’IRM fonctionnelle multiparamétrique pour l’exploration du placenta à 4.7 T chez la rate gestante. Matériel et méthode : L’IRM de diffusion (SE- EPI DWI) avec analyse IVIM et l’IRM dynamique avec injection de gadolinium (DCE) et haute résolution temporelle (< 1s) ont été développées puis étudiées sur un modèle murin contrôlé d’hypoperfusion placentaire par ligature du pédicule vasculaire utérin gauche au 17ème jour de gestation. Les paramètres obtenus sur les placentas hypoperfusés de la corne gauche ligaturée étaient comparés à ceux des placentas normaux de la corne droite. L’effet de l’hyperoxygénation maternelle était étudié en diffusion. Résultats : Ont été étudiés 73 placentas, dont 23 pathologiques (n= 10 rates) en diffusion et 53 placentas, dont 11 pathologiques (n=12 rates) en DCE. Les paramètres significativement diminués du côté hypoperfusé étaient le coefficient apparent de diffusion (ADC), la fraction de perfusion (f) en diffusion et le flux sanguin maternel (F) en DCE. Sous hyperoxygénation maternelle, l’ADC et le coefficient de diffusion (D) augmentaient et f diminuait. Les paramètres obtenus en diffusion et en DCE n’étaient pas nettement corrélés entre eux. Conclusion : Un outil d’IRM fonctionnelle placentaire multiparamétrique a été développé à 4.7 T chez la rate gestante. La DWI comme la DCE apparaissent complémentaires pour le diagnostic d’hypoperfusion placentairePlacental insufficiency caused by deficient vascularization is common during pregnancy, difficult to diagnose and can lead to severe materno-fetal complications (intrauterine growth restriction, preeclampsia). The aim of this work was to develop multi-parametric functional magnetic resonance imaging (MRI) to assess the placenta at 4.7 T on a murine model. Materials and methods : Diffusion-weighted imaging (SE-EPI-DWI) with the intravoxel incoherent motion (IVIM) analysis and dynamic contrast enhanced MRI (DCE) with a high-time resolution (<1 s) were developed and evaluated on a controlled rat model of reduced placental perfusion, achieved by ligation of the left uterine vascular pedicle on the 17th embryonic day. Parameters from the placentas in the left ligated horn were compared to those from the normal placentas in the non ligated horn. The effect of maternal hyperoxygenation on placental microvascularization was studied with DWI.Results: For DWI, 73 placentas were examined, 23 from the ligated side (n=10 rats). For DCE, 53 placentas were analysed, 11 from the ligated side (n=12 rats). In the uterine horn with reduced perfusion, the apparent diffusion coefficient (ADC), the perfusion fraction (f) obtained with DWI and the placental blood flow (F) obtained with DCE were significantly decreased. Under maternal hyperoxygenation, ADC and the diffusion coefficient (D) increased whereas f decreased. DWI and DCE parameters were not significantly correlated with each other. Conclusion: Multi-parametric MRI has been developed for murine placental analysis at 4.7T. DWI and DCE are complementary tools for the diagnosis of reduced placental perfusion
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Shang, Hongkai [Verfasser]. "Effects of maternal dexamethasone treatment early in pregnancy on glucocorticoid receptors in the ovine placenta / Hongkai Shang." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1082538183/34.
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Holder, Elizabeth. "The role of placental human endogenous retroviruses and shed microvesicles on the maternal immune system." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-placental-human-endogenous-retroviruses-and-shed-microvesicles-on-the-maternal-immune-system(a4dfe0ac-c938-4768-99d6-7f132c5aecf9).html.
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Objectives: Human Endogenous Retroviruses (HERVs) were originally derived from germ cell infection by exogenous retroviruses and comprise around eight per cent of the human genome. HERVs are highly expressed in the placenta, where HERV-W (syncytin 1) has been demonstrated to perform a fusogenic function. Due to their retroviral origin, placental syncytin 1 has been suggested to also be involved in modulating the maternal immune system. The placenta constantly sheds microvesicles (MV) into the maternal circulation, demonstrated to cause innate immune cell activation associated with normal pregnancy. In pre-eclampsia, there is both increased placental MV shedding and a heightened pro-inflammatory immune response. It was therefore hypothesised that HERVs shed via placental MV play a role in feto-maternal immune interactions and thus may be an important factor in the pathogenesis of preeclampsia (PE). More specifically, it was hypothesised that syncytin 1-positive MV activate monocytes through toll-like receptor 4 (TLR-4). The aim of this study was to determine if syncytin 1 is released from the placenta via MV and exerts an immunological effect. Methods: HERV mRNA and protein expression was measured in placenta and the BeWo choriocarcinoma cell line by qPCR, western blotting (WB) and immunostaining. Glycosylation of syncytin 1 protein was determined by PNGase F treatment followed by WB. MV shed by first trimester, term normal and PE placental explants as well as BeWo cells were isolated by ultracentrifugation. Morphology of these microvesicles was examined by electron microscopy. Syncytin 1 protein and RNA was detected in microvesicles by WB and PCR. Activation and priming of PBMCs to respond to lipopolysaccharide (LPS) by syncytin 1-positive MV and recombinant syncytin 1 was examined through cytokine production by ELISA and multiplex. Antagonism of TLR-4 by LPS-RS was used to determine involvement of the receptor. The role of syncytin 1 in MV activation was examined by siRNA knockdown. Results: HERVs are highly expressed in placental tissue. Syncytin 1 is a glycosylated protein and its expression is altered in PE. MV shed from the BeWo choriocarcinoma cell line and from first trimester and term placental explants, express HERV protein and RNA. Syncytin 1 positive MV and recombinant syncytin protein cause activation of PBMCs. Greatest activation is stimulated by PE MV. Normal MV exhibit a neutral or suppressive effect on subsequent LPS challenge to PBMCs. PE MV exacerbate the response to LPS. Antagonism of TLR-4 on PBMCs and knockdown of syncytin 1 content in MV reduces activation by placental MV.Conclusions: The findings of this thesis suggest that syncytin 1 protein expressed by the placenta is shed into the maternal circulation via MV, and can activate immune cells through TLR-4. Syncytin 1-positive microvesicles may play a role in endotoxin tolerance of innate immune cells in pregnancy. The increased activation by PE MV implies that in addition to the increased microvesicle load in this pathology, a factor intrinsic to PE MV is responsible for increased inflammation. These studies implicate microvesicle-bound syncytin 1 in the regulation of immunotolerance during pregnancy.
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Morisawa, Nobuko. "Magnetic Resonance Imaging Manifestations of Decidualized Endometriotic Cysts: Comparative Study With Ovarian Cancers Associated With Endometriotic Cysts." Kyoto University, 2015. http://hdl.handle.net/2433/199169.
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Costa, Lia Filipa Alvarez Pereira da Mota e. "Cannabinoids impact on pregnancy: effects in trophoblast cells." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15948.
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Mestrado em Biologia Molecular e CelularCannabinoids (CBs) can be classified as: phytocannabinoids, the constituents of the Cannabis sativa plant; synthetic cannabinoids lab-synthesized and the endocannabinoids that are endogenous lipid mediators. Cannabinoid compounds activate cannabinoid receptors – CB1 and CB2. The most prevalent psychoactive phytocannabinoid is Δ9tetrahydrocannabinol (THC), but more than 60 different CBs were already identified in the plant. The best characterized endocannabinoids (eCBs) are anandamide (AEA) and 2arachidonoylglycerol (2-AG), that are involved in several physiological processes including synaptic plasticity, pain modulation, energy homeostasis and reproduction. On the other hand, some synthetic cannabinoids that were initially designed for medical research, are now used as drugs of abuse. During the period of placental development, highly dynamic processes of remodeling occur, involving proliferation, apoptosis, differentiation and invasion of trophoblasts. It is known that a tight control of eCBs levels is required for normal pregnancy progression and that eCBs are involved in trophoblast cells turnover. Therefore, by sharing activation of the same receptors, exposure to exocannabinoids either by recreational or medicinal use may lead to alterations in the eCBs levels and in the endocannabinoid system homeostasis In this work, it was studied the impact of CBs in BeWo trophoblastic cells and in primary cultures of human cytotrophoblasts. Cells were treated for 24 hours with different concentrations of THC, the synthetic cannabinoid WIN‐55,212 (WIN) and 2-AG. Treatment with THC did not affect BeWo cells viability while WIN and 2-AG caused a dose-dependent viability loss. Morphological studies together with biochemical markers indicate that 2-AG is able to induce apoptosis in cytotrophoblasts. On the other hand, morphological studies after acridine orange staining suggest that autophagy may take part in WIN-induced loss of cell viability. All cannabinoids caused a decrease in mitochondrial membrane potential (Δψm) but only 2-AG led to ROS/RNS generation, though no changes in glutathione levels were observed. In addition, ER-stress may be involved in the 2-AG induced-oxidative stress, as preliminary results point to an increase in CCAAT-enhancer-binding protein homologous protein (CHOP) expression. Besides the decrease in cell viability, alterations in cell cycle progression were observed. WIN treatment induced a cell cycle arrest in G0/G1 phase, whereas 2-AG induced a cell cycle arrest in G2/M phase. Here it is reinforced the relevance of cannabinoid signaling in fundamental processes of cell proliferation and cell death in trophoblast cells. Since cannabis-based drugs are the most consumed illicit drugs worldwide and some of the most consumed recreational drugs by pregnant women, this study may contribute to the understanding of the impact of such substances in human reproduction.
Os canabinóides (CBs) podem ser classificados como: fitocanabinóides, os constituintes da planta Cannabis sativa L.; canabinóides sintéticos, sintetizados em laboratório e os endocanabinóides, que são mediadores lipídicos endógenos. Os compostos canabinóides ativam recetores canabinóides – CB1 e CB2. O composto psicoativo mais prevalente é o Δ9-tetrahidrocanabinol (THC), mas mais de 60 diferentes CBs foram já identificados a partir da planta. Os endocanabinóides (eCBs) melhor caracterizados são a anandamida (AEA) e o 2-araquidonoilglicerol (2-AG), que estão envolvidos em vários processos biológicos, incluindo plasticidade sináptica, modulação da dor, homeostasia energética e reprodução. Por outro lado, alguns canabinóides sintéticos, inicialmente projetados para investigação médica, são agora usados como drogas de abuso. Durante o período de desenvolvimento placentário ocorrem processos de remodelação que envolvem proliferação, apoptose, diferenciação e invasão dos trofoblastos. Sabe-se que um controlo rigoroso dos níveis de eCBs é necessário para uma progressão normal da gravidez e que os eCBs estão envolvidos no turnover celular dos trofoblastos. Assim sendo, ao partilharem a ativação dos mesmos recetores, a exposição a exocanabinóides, seja pelo uso recreativo ou medicinal, pode levar a alterações nos níveis de eCBs e na homeostasia do sistema endocanabinóide (ECS). Neste trabalho foi estudado o impacto dos CBs em células trofoblásticas BeWo e em culturas primárias de citotrofoblastos humanos. As células foram tratadas durante 24 horas com diferentes concentrações de THC, do canabinóide sintético WIN-55,212 (WIN) e de 2AG. O tratamento com THC não afetou a viabilidade das células BeWo, enquanto que o WIN e o 2-AG causaram uma perda de viabilidade dependente da dose. Estudos morfológicos, juntamente com marcadores bioquímicos, indicam que o 2-AG é capaz de induzir apoptose em citotrofoblastos. Por outro lado, estudos morfológicos realizados com laranja de acridina sugerem que a autofagia pode estar envolvida na perda de viabilidade induzida pelo WIN. Todos os canabinóides induziram perda de potencial de membrana mitocondrial (Δψm), mas apenas o 2-AG levou a um aumento na formação de ROS/RNS, sem terem sido observadas diferenças nos níveis de glutationa. O stress reticular pode estar envolvido no stress oxidativo induzido pelo 2-AG, visto que resultados preliminares apontam para um aumento na expressão de CCAAT-enhancer-binding protein homologous protein (CHOP). Para além da diminuição da viabilidade celular, os resultados sugerem alterações na progressão do ciclo celular. O tratamento com WIN induziu retenção do ciclo celular em fase G0/G1, enquanto que o 2-AG levou a uma retenção em fase G2/M. Neste trabalho é reforçada a importância da sinalização canabinóide em processos importantes de proliferação e morte celular de células trofoblásticas. Visto que as drogas canabinóides são as mais consumidas a nível mundial, e umas das drogas recreativas mais consumidas pelas mulheres grávidas, este estudo pode contribuir para a compreensão do impacto destas substâncias na reprodução humana.
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Nascimento, Karollina Ferreira do. "Inflamação durante a gestação: efeito da administração de lipopolissacarídeo (LPS) de Escherichia coli na expressão do fator de inibição de migração de macrófagos (MIF) na interface materno-fetal." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-13112012-104439/.
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A implantação embrionária determina eventos biológicos de fundamental importância para o desenvolvimento do embrião e para o sucesso da gestação. O fator de inibição de migração de macrófagos (MIF) é uma das muitas citocinas que atuam durante a gestação, desempenhando múltiplas funções biológicas e atividades pró-inflamatórias, em resposta a infecções ou à presença de toxinas bacterianas e estresse. Este estudo investigou a expressão de MIF na interface materno-placentária em condições infecto-inflamatórias simuladas no organismo materno pela administração de LPS de Escherichia coli, período imediatamente após a implantação embrionária. Na primeira etapa foi administrado LPS nas doses de 0,06, 0,1, 0,2 e 0,3 mg/g de peso corporal aos 7,5 dias de gestação e o perfil gestacional foi analisado. Na segunda etapa a dose mais adequada (de 0,1 mg/g) foi administrada e a gestação interrompida 30 minutos, 1, 3 e 6 após. Com esta dose observou-se diminuição o padrão de expressão protéica de MIF durante as 6 horas seguintes ao estímulo com LPS, enquanto que a expressão gênica permaneceu estável, aumentando significativamente apenas após 6 horas de tratamento.The embryo implantation determines biological events essential for embryo development and the success of pregnancy. The macrophage migration inhibitory factor (MIF) is one of many cytokines that act during pregnancy, playing multiple biological functions and pro-inflammatory activities in response to infection or the presence of bacterial toxins and stress. This study investigated the expression of MIF in the maternal-placental interface in infectious and inflammatory conditions simulated in the mother by the administration of LPS from Escherichia coli, on the period immediately after embryo implantation. In the first step LPS was administered at doses of 0.06, 0.1, 0.2 and 0.3 mg / g body weight at 7.5 day gestation and pregnancy profile was analyzed. In the second step the more appropriate dose (0.1 mg / g) was administered 30 minutes and stopped pregnancy, 1, 3 and 6 after. At this dose there was a decrease in the pattern of protein expression of MIF during the 6 hours of stimulation with LPS, while the gene expression remained stable, significantly increasing only after 6 hours of treatment.
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Martucci, Mariane Ferracin. "Expressão do complexo receptor CD74 - CD44 para o fator de inibição de migração de macrófagos (MIF) na interface materno placentária em camundongos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-26102011-142651/.
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Este estudo determinou a expressão gênica e a localização tecidual de receptores do fator de inibição da migração de macrófagos (MIF) na interface materno-placentária em camundongos aos 7,5, 10,5, 13,5 e 17,5 dias de gestação (ddg). Observou-se expressão gênica dos receptores na decídua durante todo o período estudado. CD74 e CD44 foi imunolocalizado em células deciduais, endoteliais e leucócitos, sugerindo que estas populações são presuntivos alvos do diálogo parácrino trofoblasto-decídua. No compartimento fetal, a expressão de CD74 ocorreu aos 7.5 e 17,5 ddg e de CD44, durante a gestação. RNAm dos receptores, mas não imunolocalização destes foi observada no trofoblasto aos 7,5 ddg, sugerindo mecanismos reguladores pós-transcricionais. Como a sinalização mediada por MIF requer CD74 para ativação de CD44, a baixa expressão de CD74 aos 10,5 e 13,5 ddg sugere sinalização limitada. Os resultados sugerem que a placenta fetal tem populações específicas expressando CD44-CD74 no final da gestação, o que pode ser determinante para a ativação celular mediada pelo MIF.The study determined the gene expression and tissue localization of the macrophage migration inhibitory factor (MIF) receptors (CD74-CD44) at the maternal placental interface in mice, on gestation days (gd) 7.5, 10.5, 13.5 and 17.5. We observed the gene expression of the receptors to the decidua in all gestation days. CD74-CD44 were immunolocalized in decidual and endothelial cells and, leukocytes, suggesting these cells are presumptive targets for trophoblast-decidual paracrine dialogue. In the fetal compartment, expression of CD74 occurred on gd7.5 and 17.5 and of CD44 during all pregnancy. mRNA for both receptors, but not immunolocalization was detected on the gd7.5-trophoblast, suggesting post-transcriptional regulatory mechanism. As MIF-mediated signaling requires CD74 for activation of CD44, low expression of CD74 on gd10.5 and 13.5 suggests restriction of MIF effect. The results suggest fetal placenta has specific populations expressing CD74-CD44 in the final pregnancy, which can be a determining factor in mechanisms of cellular activation mediated by MIF.
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Hirst, Chloe. "Placental taurine transport in pre-eclampsia." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/placental-taurine-transport-in-preeclampsia(85a6b6e1-f0be-46f4-bec4-22c03183ff19).html.
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Pre-eclampsia (PE) is a serious disease affecting approximately 5% of pregnancies per annum. The disease etiology is complex but its origin lies in abnormal placental development and function. PE is associated with inflammation, increased nitrative stress and abnormal renewal of syncytiotrophoblast (STB), the transporting epithelium of the placenta. STB is renewed by cytotrophoblasts (CTBs) that proliferate, differentiate and fuse with STB and this is balanced by apoptosis. The amino acid taurine facilitates proliferation, differentiation and apoptosis in non-placental tissues. Taurine is also cytoprotective, protecting cells from damage by inflammatory cytokines. Taurine is transported from maternal blood into STB by the amino acid transporter TauT. In isolated STB membranes, TauT activity is inhibited by agents that nitrate tyrosine residues. This thesis tested the hypothesis that STB TauT activity is down-regulated in PE due to post-translational modification of TauT through tyrosine nitration which lowers intracellular taurine and contributes to altered STB renewal. Placentas were collected from normal pregnancy (NP) and PE (blood pressure >140/90mmHg after 20 weeks gestation in previously normotensive women plus proteinuria >300 mg/L in a 24-hour collection). STB TauT activity, measured as Na+-dependent uptake of 3H-taurine into placental villous fragments, was significantly lower in PE (n=24) compared to NP (n=44). Western blotting of membrane enriched homogenates showed that TauT protein expression (normalised to β-actin) was significantly higher in placentas from PE (n=8) compared to NP (n=9). The presence of nitrotyrosine residues (marker of nitrative stress) in placentas of women with PE and NP was assessed by immunohistochemistry (IHC). The intensity of STB nitrotyrosine staining was greater in PE placentas that had reduced TauT activity (n=8) than in NP (n=7). To determine the effect of nitrative stress on TauT activity and STB renewal, placental villous explants from NP were cultured (7 days; n=6) and treated with SIN-1 (1mM; days 5,6) to induce nitrative stress. STB nitrotyrosine (IHC) and TauT activity (3H-taurine uptake) was determined on day 7 and STB renewal was assessed by IHC for apoptosis (M30), proliferation (dual staining for Ki67 and the CTB marker E-cadherin) and STB integrity (cytokeratin 7). SIN-1 increased STB nitrotyrosine staining intensity compared to controls, confirming induction of nitrative stress. SIN-1 reduced STB TauT activity, increased apoptosis, reduced CTB proliferation and altered STB regeneration compared to control. To determine the effect of reducing intracellular taurine on STB renewal, villous explants were cultured for 7 days with 2.5mM β-alanine to competitively inhibit taurine uptake (n=6). At day 7, intracellular taurine, measured as the steady-state accumulation of 3H-taurine, was 15% of normal. STB turnover was assessed at day 7 as described above. β-alanine significantly increased apoptosis and altered STB regeneration compared to controls. Following statistical analysis all p <0.05.In conclusion, STB TauT activity was lower, and protein expression higher, in PE compared to NP. STB nitrotyrosine was elevated in PE and nitrative stress inhibited STB TauT activity and disrupted STB renewal in vitro. Reducing intracellular taurine also disrupted STB renewal in vitro. Overall the data support the hypothesis that post-translational modification of TauT by nitration inhibits TauT activity in PE. This reduces intracellular taurine which contributes to abnormal renewal of STB. Further work is needed (a) to confirm that TauT is nitrated in PE and that reduced STB TauT activity lowers intracellular taurine and reduces taurine delivery to the fetus and (b) to determine the mechanism/s by which taurine regulates CTB apoptosis and facilitates renewal of STB.
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Nasiell, Josefine. "Expression and regulation of vasoactive substances, sex steroids and their receptors in placenta during normal pregnancy and preeclampsia /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-154-3.
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Chowdhury, Nishat Nailah. "Mother's weight gain during pregnancy and its effect on the gene expression of lipoprotein lipase in the placenta." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-441608.
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It has been found in previous studies that there is a correlation between the placenta regulatory genes and the weight gain of the mother, Body Mass Index (BMI) as well as the birthweight of the fetus. When the mother gains weight / is overweight, this will affect the gene expression in the placenta, and in turn this triggers the weight gain of the fetus. The aim of the study was to investigate the correlation between the lipoprotein lipase gene and the mother's BMI, weight gain and the child's birth weight by extracting RNA from the placentas and analysing its quality and concentration. cDNA was generated from RNA using reverse transcription and gene expression was amplified using real-time PCR. The data from real-time PCR was used in the comparative Ct-method to calculate a 2˄(-ΔΔCt)-value which represents the RNA-level of the LPL-gene. Lastly this value was analysed by using the two-statistic methods, Pearson's rank correlation and Spearman's correlation, which showed that the value of the correlation coefficient for all the variables was close to the value of zero. The closer the value is to zero, the weaker the association becomes between the different variables. The correlation was 0.045, 0.112 and 0.044 for the child's birth weight, mother's BMI respective weight gain. The results from this study shows that there is no correlation between LPL and the mother's weight gain, BMI, or the child's birth weight.
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Macchiaverni, Patricia. "Caracterização quantitativa e funcional da transferência de anticorpos anti-Dermatophagoides pteronyssinus via placenta e colostro materno." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-18092008-112302/.
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Existem fortes evidências de que a supressão da hipersensibilidade nos recém nascidos pode ser mediada pela transferência de anticorpos maternos, dependendo de sua concentração e especificidade, no entanto carece estudos sobre a eficácia em humanos. Realizamos este estudo a fim de caracterizar qualitativa e quantitativamente a transmissão de anticorpos direcionados ao principal alérgeno da poeira domiciliar (Der p) via placenta e colostro materno, assim como investigar o efeito da sensibilização materna ao Der p na transferência passiva destes anticorpos. Para tais objetivos, analisamos amostras de sangue materno, cordão umbilical e colostro de puérperas sensibilizadas. Demonstramos pela primeira vez que S-IgA anti-Der p pode ser transferida ao lactente em concentrações bastante variáveis e com alto índice de avidez, independente da sensibilização materna ao mesmo ácaro. Demonstramos também que o nível de IgG específica ao Der p é mais elevado em recém nascidos de mães sensibilizadas quando comparado aos de mães controle não sensibilizadas. Já a avidez específica da IgG anti-Der p foi muito semelhante entre as amostras pareadas de cordão umbilical e soro materno, assim como em amostras do grupo estudo e grupo controle.It is known that the incidence of allergic disease has been rising very fast in the last decade and nowadays affects thousands of children worldwide. For this reason, it is of great interest that efficient strategies of prevention of atopy should be applied in the first years of life or even before birth. The are strong evidences that the suppression of hypersensitivity in newborn can be mediated by the transference of maternal antibodies, depending on their concentration and specificity, however still little is known about the mechanisms involving, in special in humans. We made this study aiming to characterize qualitatively and quantitatively the antibodies transmission directed to the main home dust allergen (Dermatophagoides pteronyssinus; Der p) through placental transference and maternal breastfeeding as well as to investigate the maternal sensitizing effect against to Der p in passive transference of these antibodies. For those objectives, we quantified by ELISA, IgG anti-Der p in paired samples of maternal blood and umbilical cord and anti-Der p S-IgA in colostrums of sensitized mother (n=13) and not sensitized (n=26); and we analyzed the functional activity of the same antibodies by avidity assays. The sensibility was determined in maternal sera by specific RAST (Cap System® Pharmacia). We show by the first time that anti-Der p S-IgA is transferred to the infant in very variable concentrations and with high levels of avidity, but is not dependent of maternal sensitization. We believe that breastfeeding is important, because it supplies S-IgA with the capacity to neutralize in a specific manner and block the entrance of Der p through mucosa, in infant of RAST+ mothers as well as of RAST-. We also demonstrate that total and specific to Der p IgG levels are more elevated in newborns of sensitized mothers when compared to of those of control mothers and non-sensitized indicating that the maternal sensitizing can influence the fetal immune response. In the other hand, the specific avidity of anti-Der p IgG was very similar between paired samples of umbilical cord and maternal sera, as well as in samples of study group and control group, suggesting thar the avidity index of IgG does not influence on placental transfer of specific antibodies. Once that the maternal antibody transference represent a important mechanism for immunomodulation of allergic response, we expect that a better understanding of the influence of maternal sensitivity on passive transfer of specific antibodies to babies will contribute with advances in the elaboration of adequate strategies of prevention of allergic sensitivity with more efficient therapeutic results.
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Deloison, Benjamin. "Imagerie fonctionnelle placentaire par résonance magnétique : étude de la perfusion placentaire." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112256.
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L’insuffisance placentaire est une pathologie grave avec un diagnostic souvent trop tardif empêchant la mise en place de thérapeutiques efficaces. Le but de ce travail de Thèse est de développer chez la rate gestante et de transposer à l’Homme des outils d’IRM fonctionnelle (IRMf) placentaire qui permettrait une quantification de la perfusion placentaire en pratique clinique.Matériels et méthodes : Trois études en IRMf font partie de cette Thèse.Les deux premières ont été réalisées sur un modèle murin. Une séquence dynamique avec injection d’un agent de contraste (DCE) a été développée avec une particule de fer de type SPIO dans un modèle chirurgical d’hypoperfusion placentaire chronique, avec mesure de la perfusion placentaire f en ml/min/100ml et de la fraction volumique (Vb) en %. Une autre technique d’IRMf a été développée avec l’Arterial Spin Labeling (ASL) permettant d’estimer la perfusion placentaire en ml/min/100g sans injection de produit de contraste exogène. La dernière étude était une recherche translationnelle. Elle a consisté au développement de séquences de DCE avec injection de chélate de gadolinium, pour obtenir la perfusion f en ml/min/100ml et la fraction volumique en %. Nous avons également étudié, au décours de cette étude, la pharmacocinétique materno-fœtale du chélate de gadolinium.Résultats : Chez l’animal en DCE avec SPIO, notre étude nous a permis de montrer qu'il était possible d'utiliser l’effet T1 des SPIO pour caractériser la microcirculation placentaire par f=159,4 ml/min/100ml (+/- 54,6) et Vb =39,2% (+/- 11,9) pour 31 placentas « normaux ». En cas de RCIU, f diminue significativement pour les 23 placentas étudiés (f= 108,1 ml/min/100ml +/- 41, p=0,004), alors que la fraction volumique placentaire n'est pas modifiée (Vb=42,8% +/- 16,7, p=0,24). L’ASL nous a permis d’estimer la perfusion placentaire pour 47 placentas en condition physiologique, avec une perfusion estimée à 146,8 ml/min/100g (+/- 70,1).Chez l’Homme, 14 placentas ont été étudiés avec une perfusion placentaire globale estimée à 183 ml/min/100ml (+/-144) et nous avons également mis en évidence deux types de cinétique de rehaussement placentaire (précoce et intense et plus tardif et moins intense). La pharmacocinétique nous a permis d'étudier quantitativement le passage du chélate de gadolinium chez le fœtus. Ce passage est faible: par rapport à la concentration initiale du Dotarem®, la concentration sanguine fœtale correspond à 18,1x10-6 %, la concentration dans le liquide amniotique à 242,8 x10-6 % et 0,3 % de la dose initiale de Dotarem® est présente dans le placenta environ 70 heures après l’injection.Conclusion : Ce travail illustre la variété des techniques d'IRM fonctionnelle disponibles pour l'étude du placenta. La perfusion placentaire peut être quantifiée en DCE avec un agent particulaire à base de fer (SPIO) ou sans injection de produit de contraste en ASL chez le rat. L’étude de la perfusion placentaire chez l'Homme est possible en DCE avec les chélates de gadolinium.Mots clés : IRM, DCE, chélates de Gadolinium, ASL, perfusion placentaire, grossesse, placenta, retard de croissance intra-utérinPlacental insufficiency is a serious medical condition with a diagnosis made usually too late to prevent introduction of effective therapies. The aim of this thesis is to develop, in pregnant rats and translate to humans, functional MRI (fMRI) tools allowing quantification of placental perfusion in clinical practice.Materials and Methods: Three studies using fMRI are part of this thesis. The first two were performed on a murine model. A dynamic sequence with injection of a contrast agent (DCE) has been developed with an iron oxide particle (SPIO) in a surgical model of chronic placental hypoperfusion with placental perfusion measurement (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. Another technique of fMRI was developed with Arterial Spin Labeling (ASL) to estimate placental perfusion in ml / min / 100g without injection of contrast media.The latest study was a translational research. It consisted in the development of a dynamic sequence with injection of gadolinium chelate, in order to obtain perfusion (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. We also studied maternal and fetal pharmacokinetics of gadolinium chelate.Results: In animals with SPIO DCE, our study allowed us to show that it is possible to use the T1 effect of SPIO to characterize the placental microcirculation by f = 159.4 ml / min / 100ml (+ / - 54.6) and Vb = 39.2% (11.9 +/-) for 31 « normal » placentas. In case of IUGR, f decreases significantly for the 23 examined placentas (f = 108.1 ml / min / 100ml +/- 41, p = 0.004), whereas the volume fraction placenta is not modified (Vb = 42 +/- 16.7 8 %, p = 0.24). ASL has allowed us to estimate placental perfusion for 47 placentas under physiological conditions, with an estimated perfusion of 146.8 ml / min / 100 g (70.1 +/-).In humans, 14 placentas were studied with an estimated perfusion of 183 ml / min / 100ml (+/- 144) and we also identified two types of placental kinetic enhancement (early and intense and later and less intense). Pharmacokinetics have allowed us to study quantitatively the transfer of gadolinium chelate in the fetus. This transfer is low compared to the initial concentration of Dotarem® : fetal blood concentration is 18.1x10-6%, concentration in amniotic fluid is 242.8 x10-6 % and 0.3% of the Dotarem® initial dose is present in the placenta approximately 70 hours after injection.Conclusion: This study illustrates the variety of functional MRI techniques available for placental study. Placental perfusion can be quantified by DCE with an iron oxide particle (SPIO) or without injection of contrast in ASL, in a rat model. The study of placental perfusion in humans is also possible in DCE with gadolinium chelates