Journal articles on the topic 'Placental hypoxia'
To see the other types of publications on this topic, follow the link: Placental hypoxia.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Placental hypoxia.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Stanek, Jerzy. "Diagnosing Placental Membrane Hypoxic Lesions Increases the Sensitivity of Placental Examination." Archives of Pathology & Laboratory Medicine 134, no. 7 (July 1, 2010): 989–95. http://dx.doi.org/10.5858/2009-0280-oa.1.
Full textAbstract:
Abstract Context.—Two relatively unknown and recently described placental membrane hypoxic lesions (laminar necrosis and microscopic chorionic pseudocysts) have never been compared with time-honored, focal (infarction), and diffuse hypoxic lesions of placental parenchyma. Objective.—To compare the effect on placental diagnosis of the above placental membrane hypoxic lesions and chorionic disc hypoxic lesions (infarctions and global hypoxic pattern of placental injury). Design.—Twenty-three clinical (maternal and fetal) and 32 gross and microscopic placental features were retrospectively compared in 4590 placentas from a placental database built during a 13-year period: 168 placentas with at least one hypoxic disc lesion (infarct or global hypoxia) and at least one membrane lesion (microscopic chorionic pseudocysts or laminar necrosis (group 1), 750 placentas with at least one hypoxic villous lesion but no membrane lesion (group 2), 480 placentas with at least one membrane lesion but no villous lesion (group 3), and 3192 placentas with no hypoxic villous or membrane lesions (group 4). Results.—Several clinical and fetal conditions and placental features known to be associated with in utero hypoxia had a statistically significant correlation with the index hypoxic placental lesions, both villous and membranous. Of placentas from patients associated with clinical conditions at risk for hypoxia, 15% featured only hypoxic membrane lesions without a chorionic disc hypoxic lesion. Conclusions.—Recognizing placental membrane hypoxic lesions increases the sensitivity of placental examination in diagnosing placental hypoxia by at least 15%. The risk of in utero hypoxia is increased when microscopic chorionic pseudocysts and laminar necrosis occur in conjunction with villous hypoxic lesions.
2
Tissot van Patot, M. C., J. Bendrick-Peart, V. E. Beckey, N. Serkova, and L. Zwerdlinger. "Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia." American Journal of Physiology-Lung Cellular and Molecular Physiology 287, no. 3 (September 2004): L525—L532. http://dx.doi.org/10.1152/ajplung.00203.2003.
Full textAbstract:
Vascularity is increased in placentas from high- compared with low-altitude pregnancies. An angiogenic response to hypoxia may protect an organ from further hypoxic insult by increasing blood flow and oxygen delivery to the tissue. We hypothesized that increased placental vascularity is sufficient to adapt to high altitude. Therefore, indexes of hypoxic stress would not be present in placentas from successful high-altitude pregnancies. Full-thickness placental biopsies were 1) collected and frozen in liquid nitrogen within 5 min of placental delivery and 2) fixed in formalin for stereologic analyses at high (3,100 m, n = 10) and low (1,600 m, n = 10) altitude. Hypoxia-inducible transcription factor (HIF-1) activity was analyzed by ELISA. Western blot analyses were used to evaluate HIF-1α, HIF-1β, HIF-2α, von Hippel-Lindau protein, VEGF, Flt-1, enolase, and GAPDH. Magnetic resonance spectroscopy was used to evaluate endogenous metabolism. The ratio of placental capillary surface density to villous surface density was 70% greater at high compared with low altitude. HIF-1 activity and HIF-1-associated proteins were unchanged in placentas from high- vs. low-altitude pregnancies. Placental expression of HIF-1-mediated proteins VEGF, Flt-1, enolase, and GAPDH were unchanged at high vs. low altitude. Succinate, GSH, phosphomonoesters, and ADP were elevated in placenta from high compared with low altitude. Placentas from uncomplicated high-altitude pregnancies have greater vascularity and no indication of significant hypoxic stress at term compared with placentas from low altitude.
3
GUDE, N. M., J. L. STEVENSON, E. K. MOSES, and R. G. KING. "Magnesium regulates hypoxia-stimulated apoptosis in the human placenta." Clinical Science 98, no. 4 (February 24, 2000): 375–80. http://dx.doi.org/10.1042/cs0980375.
Full textAbstract:
Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased levels of placental apoptosis. Altered regulation of apoptosis may play an important pathophysiological role in FGR. As reduced placental perfusion and reduced oxygenation are features of FGR, one aim of this study was to determine the effects of hypoxia on apoptotic activity, as assessed by DNA laddering, of placental tissue in vitro. In addition, levels of placental apoptosis may be affected by pharmacological agents routinely used in obstetric patient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA laddering during in vitro incubation of human placentae under hypoxic conditions. Incubation of normal placental explant tissue at 37 °C for 1–2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not significantly higher than those in non-incubated tissue. The DNA laddering activity of placental explants after 2 h of incubation under hypoxic conditions was significantly increased with increased concentrations of magnesium, but remained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexamethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human placental tissues, and that hypoxia-stimulated placental apoptosis may be further increased by increasing the extracellular magnesium concentration.
4
Tong, Wen, Beth J. Allison, Kirsty L. Brain, Olga V. Patey, Youguo Niu, Kimberley J. Botting, Sage G. Ford, et al. "Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring." Hypertension 79, no. 7 (July 2022): 1525–35. http://dx.doi.org/10.1161/hypertensionaha.122.19175.
Full textAbstract:
Background: Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology. Methods: We adopted an integrative approach to investigate the inter-relationship between chronic hypoxia during pregnancy with maternal, placental, and fetal outcomes, common in preeclampsia. We exploited a novel technique using isobaric hypoxic chambers and in vivo continuous cardiovascular recording technology for measurement of blood pressure in sheep and studied the placental stress in response to hypoxia at cellular and subcellular levels. Results: Chronic hypoxia in ovine pregnancy promoted fetal growth restriction (FGR) with evidence of fetal brain-sparing, increased placental hypoxia-mediated oxidative damage, and activated placental stress response pathways. These changes were linked with dilation of the placental endoplasmic reticulum (ER) cisternae and increased placental expression of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase 1) and sEng (soluble endoglin), combined with a shift towards an angiogenic imbalance in the maternal circulation. Chronic hypoxia further led to an increase in uteroplacental vascular resistance and the fall in maternal blood pressure with advancing gestation measured in normoxic pregnancy did not occur in hypoxic pregnancy. Conclusions: Therefore, we show in an ovine model of sea-level adverse pregnancy that chronic hypoxia recapitulates physiological and molecular features of preeclampsia in the mother, placenta, and offspring.
5
Mikhaylin, Evgeny S., Gulrukhsor K. Tolibova, and Tatyana G. Tral. "Morfological and functional features of placentas in minor women." Journal of obstetrics and women's diseases 65, no. 5 (September 15, 2016): 41–48. http://dx.doi.org/10.17816/jowd65541-48.
Full textAbstract:
Relevance. An in-depth study of the state of feto-placental complex, the characteristics of its reactions in response to hypoxia on the background of juvenile immaturity of minors can help to identify the main directions of the prevention of certain complications of pregnancy and childbirth among minors in the first place — placental insufficiency, preeclampsia, fetal hypoxia. Purpose of the study was to explore features of the histological structure of placentas and expression of HIF-1α and VEGF-A markers in placentas in minors.Materials and methods. 74 placentas from minors were investigated by histological methods. The comparison group consisted of 25 placentas from healthy women the average reproductive age (20-30 years). The immunohistochemical study was performed in 35 placentas from minors who were divided into groups according to age and the presence or absence of chronic placental insufficiency. To study vascular status of villous tree of placentas were used the monoclonal antibodies of the vascular endothelial growth factor VEGF-A (Clone UG1; 1 : 50, Dako), to assess hypoxia in placenta were used the monoclonal antibodies of hypoxia — inducible factor HIF-1α (H1 alpha 67; 1 : 100, GRTP (Abcam).Results. It was revealed that the placenta in minors is characterized by hypertrophy (559,5 ± 10,5 g vs. 478,7 ± 12,9 g), it is pathologically immature (33,8% vs. 7,0%), there is significantly greater frequency of chronic placental insufficiency in minors (33,8% versus 4,0%) with significantly lower severity of compensatory-adaptive reactions (86,5% vs. 100%). It is shown increased expression of hypoxia — inducible factor (HIF-1) and vascular endothelial growth factor-A (VEGF-A) in placentas of minor women with chronic placental insufficiency, compared with placentas of minor women without chronic placental insufficiency.Conclusion. Chronic placental insufficiency at the time of birth, detectable more frequently in minor patients can make a difference in violation of adaptive mechanisms and quality of life of children in the postnatal period. Increased expression of HIF-1α and VEGF-A in the placentas of minor women with chronic placental insufficiency reflects activation of angiogenesis in response to intrauterine fetal hypoxia in chronic placental insufficiency.
6
Stanek, Jerzy. "Hypoxic Patterns of Placental Injury: A Review." Archives of Pathology & Laboratory Medicine 137, no. 5 (May 1, 2013): 706–20. http://dx.doi.org/10.5858/arpa.2011-0645-ra.
Full textAbstract:
Context.—In utero hypoxia is an important cause of perinatal morbidity and mortality and can be evaluated retrospectively to explain perinatal outcomes, to assess recurrence risk in subsequent pregnancies, and to investigate for medicolegal purposes by identification of many hypoxic placental lesions. Definitions of some placental hypoxic lesions have been applied relatively liberally, and many of them are frequently underreported. Objectives.—To present a comprehensive assessment of the criteria for diagnosing acute and chronic histologic features, patterns, and lesions of placental and fetal hypoxia and to discuss clinicopathologic associations and limitations of the use thereof. The significance of lesions that have been described relatively recently and are not yet widely used, such as laminar necrosis; excessive, extravillous trophoblasts; decidual multinucleate extravillous trophoblasts; and, most important, the patterns of diffuse chronic hypoxic preuterine, uterine, and postuterine placental injury and placental maturation defect, will be discussed. Data Sources.—Literature review. Conclusions.—The placenta does not respond in a single way to hypoxia, and various placental hypoxic features should be explained within a clinical context. Because the placenta has a large reserve capacity, hypoxic lesions may not result in poor fetal condition or outcome. On the other hand, very acute, in utero, hypoxic events, followed by prompt delivery, may not be associated with placental pathology, and many poor perinatal outcomes can be explained by an etiology other than hypoxia. Nevertheless, assessment of placental hypoxic lesions is helpful for retrospective explanations of complications in pregnancy and in medicolegal investigation.
7
Schäffer, Leonhard, Johannes Vogel, Christian Breymann, Max Gassmann, and Hugo H. Marti. "Preserved placental oxygenation and development during severe systemic hypoxia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290, no. 3 (March 2006): R844—R851. http://dx.doi.org/10.1152/ajpregu.00237.2005.
Full textAbstract:
Local tissue oxygenation profoundly influences placental development. To elucidate the impact of hypoxia on cellular and molecular adaptation in vivo, pregnant mice at embryonic days 7.5–11.5 were exposed to reduced environmental oxygen (6–7% O2) for various periods of time. Hypoxia-inducible factor (HIF)-1α mRNA was highly expressed in the placenta, whereas HIF-2α was predominantly found in the decidua, indicating that HIF-1 is a relevant oxygen-dependent factor involved in placental development. During severe hypoxia, HIF-1α protein was strongly induced in the periphery but, however, not in the labyrinth layer of the placenta. Accordingly, no indication for tissue hypoxia in this central area was detected with 2-(2-nitro-1 H-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)acetamide staining and VEGF expression as hypoxic markers. The absence of significant tissue hypoxia was reflected by preserved placental architecture and trophoblast differentiation. In the search for mechanisms preventing local hypoxia, we found upregulation of endothelial nitric oxide synthase (NOS) expression in the labyrinth layer. Inhibition of NOS activity by Nω-nitro-l-arginine methyl ester application resulted in ubiquitous placental tissue hypoxia. Our results show that placental oxygenation is preserved even during severe systemic hypoxia and imply that NOS-mediated mechanisms are involved to protect the placenta from maternal hypoxia.
8
Jeung, E. B., and H. Yang. "81 MEMBRANE AND CYTOSOLIC CALCIUM PROTEINS, TRPV6, PMCA1, NCKX3, NCX1 AND CaBP-28k, APPEAR TO BE DISTINCTLY REGULATED IN HUMAN CHORIOCARCINOMA AND PLACENTAL CELLS." Reproduction, Fertility and Development 24, no. 1 (2012): 153. http://dx.doi.org/10.1071/rdv24n1ab81.
Full textAbstract:
Preeclampsia is a pregnancy-specific disease characterised by de novo development of concurrent hypertension, proteinuria and oxidative stress in the placenta. In the placenta, intervillous blood flow increases after 10 weeks of gestation and results in exposure of trophoblast cells to oxygen. Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Ca2+ is a universal intracellular second messenger involved in many processes such as signal transduction, hormone secretion and programmed cell death. Human placental primary cell cultures were established from first-trimester human placentas (at 7 to 12 weeks of gestation). In this study, calcium-related proteins (CRPs; TRPV6, PMCA1, NCKX3 and CaBP-28k) were investigated at normoxia (5% CO2 in 95% air) or hypoxia (2% O2/93% N2/5%CO2) for 12 h in human placental cell line (BeWo) and human placental primary cell (hPC). We confirmed mRNA expression by real-time PCR and protein expression by Western blot analysis. The data were 2 or 3 individual experiments with triplicate samples and analysed by one-way ANOVA using Tukey's multiple comparison test. In hypoxia, the level of TRPV6 mRNA and protein was not changed, however, calcium transporters' (NCKX3, CaBP-28k) mRNA and protein expressions were significantly increased in hypoxic BeWo cell compared with control (normoxia). In addition, expression of PMCA1 mRNA and protein was decreased in hypoxic BeWo cells. In hPC, CRPs (TRPV6, PMCA1, NCKX3 and CaBP-28k) mRNA and protein expressions were significantly induced by hypoxic stress compared with control. These results, taken together, indicate that alterations of calcium transporters in hypoxic stress may be involved in calcium transport in the placenta and protection of the placental trophoblasts from the oxidative stress during the pregnancy.
9
Kartini, K., Ahmad A. Jusuf, Sri Widia A. Jusman, M. Ekawati, and Ani R. Prijanti. "Fetal blood vessel count increases in compensation of hypoxia in premature placentas." Universa Medicina 34, no. 1 (February 26, 2016): 35. http://dx.doi.org/10.18051/univmed.2015.v34.35-42.
Full textAbstract:
BACKGROUND Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. METHODS An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. RESULTS Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15)] as compared with the non-hypoxic group [7.50 (3-15)]. CONCLUSION The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.
10
Edwin, Kartini. "Hypoxic Status Is Associated With The Intensity Of Hypoxia Inducible Factor (Hif)-1α Expression In A Premature Placenta." Saintika Medika 17, no. 1 (June 9, 2021): 1–11. http://dx.doi.org/10.22219/sm.vol17.smumm1.11685.
Full textAbstract:
Prematurity refers to live births before 37 weeks of gestation and associated with infant morbidity/mortality. Activation of HIF during the final pregnancy phase is believed to play a critical role in the pathogenesis of premature birth and other pregnancy disorders. This study aimed to analyze the relationship between hypoxicstatus and the intensity of HIF-1α expression in a premature placenta.Stored biological materials premature placenta (paraffin blocks) was used in this study. Thirtyone samples of placental hypoxia (H) and 28 samples of premature placental non-hypoxia (N) as controls, were selected non-random consecutively. Subsequently, immunohistochemistry was performed to analyze HIF-1α expression. TheChi-square testwas used to analyze the data and a p-value <0.05 was considered statistically significant.Moderate to strong intensity of HIF-1α expressionwas observed in 58% of hypoxic placenta samples, whereas most of non-hypoxic placental samples(86%) did not expressed or expressed weaklyHIF-1α.There was a significant correlation between the intensity of HIF-1α expression and placental hypoxia (p <0.05) and Odds Ratio (OR) value was 8.31 with a 95% confidence interval (2.32-29.77). The conclusion shows that hypoxic status is associated with intensity of hypoxia inducible factor (HIF)-1α expression in a premature placenta.
11
Macintire, Kate, Laura Tuohey, Louie Ye, Kirsten Palmer, Michael Gantier, Stephen Tong, and Tu'uhevaha J. Kaitu'u-Lino. "PAPPA2 is increased in severe early onset pre-eclampsia and upregulated with hypoxia." Reproduction, Fertility and Development 26, no. 2 (2014): 351. http://dx.doi.org/10.1071/rd12384.
Full textAbstract:
Severe early onset pre-eclampsia is a serious pregnancy complication, believed to arise as a result of persistent placental hypoxia due to impaired placentation. Pregnancy-associated plasma protein A2 (PAPPA2) is very highly expressed in the placenta relative to all other tissues. There is some evidence that PAPPA2 mRNA and protein are increased in association with pre-eclampsia. The aim of the present study was to characterise the mRNA and protein expression, as well as localisation, of PAPPA2 in an independent cohort of severe early onset pre-eclamptic placentas. We also examined whether exposing placental explants to hypoxia (1% oxygen) changed the expression of PAPPA2. Expression of PAPPA2 mRNA and protein was upregulated in severe early onset pre-eclamptic placentas compared with preterm controls and localised to the syncytiotrophoblast. Interestingly, protein localisation was markedly reduced in term placenta. Syncytialisation of BeWo cells did not change PAPPA2 expression. However, hypoxia upregulated PAPPA2 mRNA and protein expression in primary placental explants. Together, our data suggest that PAPPA2 may be upregulated in severe pre-eclampsia and, functionally, this may be mediated via increased placental hypoxia known to occur with this pregnancy disorder.
12
Nishimoto, Fumihito, Masahiro Sakata, Ryoko Minekawa, Yoko Okamoto, Asako Miyake, Aki Isobe, Toshiya Yamamoto, et al. "Metal Transcription Factor-1 Is Involved in Hypoxia-Dependent Regulation of Placenta Growth Factor in Trophoblast-Derived Cells." Endocrinology 150, no. 4 (November 20, 2008): 1801–8. http://dx.doi.org/10.1210/en.2008-0949.
Full textAbstract:
Placenta growth factor (PlGF) is a placental angiogenic factor. Metal-responsive transcription factor (MTF)-1 was reported to take part in the hypoxic induction of PlGF in RAS-transformed mouse fibroblasts. We contrarily showed that PlGF mRNA and protein levels decreased under hypoxia in a choriocarcinoma BeWo cell line derived from trophoblast. In this report, we examined whether hypoxia-dependent regulation of the PlGF gene in these cells also depends on MTF-1. We analyzed the effect of hypoxia on MTF-1 expression, and it was revealed to be decreased. Moreover, MTF-1 small interfering RNA treatment decreased PlGF mRNA level. To investigate the transcription of PlGF under hypoxia, we cloned promoter region of the human PlGF. Promoter deletion analysis suggested that triple repeats of metal-responsive element located between −511 and −468 bp in the promoter are important for the hypoxic regulation of PlGF. Treatment with MTF-1 small interfering RNA resulted in the significant decreased luciferase activity in PlGF reporter constructs. Chromatin immunoprecipitation showed the binding of the MTF-1 protein to the promoter region. We examined MTF-1 immunoreactivity in trophoblasts of term placental tissue from patients with normal pregnancies and preeclampsia, which represents a condition of placental hypoxia. Immunoreactivity of the MTF-1 protein was decreased in placentas from pregnant women with preeclampsia when compared with those from normal pregnant women. Taken together, these findings suggest that MTF-1 is involved in hypoxia-dependent regulation of PlGF in trophoblast-derived cells.
13
Chang, Yao-Lung, Shuenn-Dyh Chang, An-Shine Chao, Martin Sieber, Chia-Lung Tsai, and Po-Jen Cheng. "Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses." Genes 13, no. 5 (April 25, 2022): 752. http://dx.doi.org/10.3390/genes13050752.
Full textAbstract:
(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expressions of GLUT1 and GLUT3 under hypoxia conditions were higher in placental mesenchymal stem cells derived from appropriate-for-gestational-age fetuses than in those from selective intrauterine growth-restricted fetuses. However, the protein expression of hypoxia induced factor-1 α (HIF-1α) at hypoxia condition was not lower in placenta mesenchymal stem cells from selective intrauterine growth-restricted fetuses than in placental mesenchymal stem cells from appropriate-for-gestational-age fetuses. (4) Conclusions: Hypoxia-induced upregulation of GLUT1 and GLUT3 expression was decreased in placental mesenchymal stem cells from selective intrauterine growth-restricted fetuses but not due to decreased HIF-1α expression. Selective growth-restricted fetuses have less capacity for hypoxia-induced upregulation of placental glucose transport.
14
Chang, Yao-Lung, Shuenn-Dyh Chang, An-Shine Chao, Martin Sieber, Chia-Lung Tsai, and Po-Jen Cheng. "Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses." Genes 13, no. 5 (April 25, 2022): 752. http://dx.doi.org/10.3390/genes13050752.
Full textAbstract:
(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expressions of GLUT1 and GLUT3 under hypoxia conditions were higher in placental mesenchymal stem cells derived from appropriate-for-gestational-age fetuses than in those from selective intrauterine growth-restricted fetuses. However, the protein expression of hypoxia induced factor-1 α (HIF-1α) at hypoxia condition was not lower in placenta mesenchymal stem cells from selective intrauterine growth-restricted fetuses than in placental mesenchymal stem cells from appropriate-for-gestational-age fetuses. (4) Conclusions: Hypoxia-induced upregulation of GLUT1 and GLUT3 expression was decreased in placental mesenchymal stem cells from selective intrauterine growth-restricted fetuses but not due to decreased HIF-1α expression. Selective growth-restricted fetuses have less capacity for hypoxia-induced upregulation of placental glucose transport.
15
Eddy, Adrian C., Heather Chapman, and Eric M. George. "Acute Hypoxia and Chronic Ischemia Induce Differential Total Changes in Placental Epigenetic Modifications." Reproductive Sciences 26, no. 6 (September 17, 2018): 766–73. http://dx.doi.org/10.1177/1933719118799193.
Full textAbstract:
Preeclampsia is a common obstetrical complication, hallmarked by new-onset hypertension. Believed to result from placental insufficiency and chronic placental ischemia, the symptoms of preeclampsia are caused by release of pathogenic factors from the placenta itself, although the mechanisms of their regulation are in many cases unknown. One potential mechanism is through changes in placental epigenetic chromatin modifications, particularly histone acetylation and DNA methylation. Here, we determined the effects of chronic ischemia on global epigenetic modifications in the rodent placenta in vivo and acute hypoxia in BeWo placental trophoblast cells in vitro. Placental insufficiency via uterine artery restriction increased maternal blood pressure and fetal demise while decreasing placental and fetal mass. Global placental histone H3 acetylation levels were significantly decreased at H3 K9, K14, K18, K27, and K56. Interestingly, when BeWo-immortalized placental trophoblast cells were cultured in oxygen concentrations mimicking healthy and ischemic placentas, there was a significant increase in acetylated at K9, K18, K27, and K56. This was associated with a small but significant decrease in placental acetyl-CoA, suggesting depletion in the source of acetyl group donors. Finally, while global methylation of cytosine from placental DNA was low in both groups of animals (<1%), there was ∼50% increase in 5-mC in response to chronic ischemia. This suggests acute hypoxia and chronic ischemia induce differential global changes in histone acetylation in the placenta and that chronically altered metabolic profiles could affect histone acetylation in the placenta, thereby regulating production of pathogenic factors from the placenta during preeclampsia.
16
Soleymanlou, Nima, Igor Jurisica, Ori Nevo, Francesca Ietta, Xin Zhang, Stacy Zamudio, Martin Post, and Isabella Caniggia. "Molecular Evidence of Placental Hypoxia in Preeclampsia." Journal of Clinical Endocrinology & Metabolism 90, no. 7 (July 1, 2005): 4299–308. http://dx.doi.org/10.1210/jc.2005-0078.
Full textAbstract:
Abstract Background: Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease. Design: Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps. Results: Our results highlight a striking global gene expression similarity between 3% O2-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia. Conclusion: Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.
17
Trollmann, Regina, Katja Strasser, Stephan Keller, Xenia Antoniou, Beat Grenacher, Omolara O. Ogunshola, Jörg Dötsch, Wolfgang Rascher, and Max Gassmann. "Placental HIFs as markers of cerebral hypoxic distress in fetal mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 295, no. 6 (December 2008): R1973—R1981. http://dx.doi.org/10.1152/ajpregu.00053.2008.
Full textAbstract:
Reduced oxygen supply during the pre- and perinatal period often leads to acquired neonatal brain damage. So far, there are no reliable markers available to assess the hypoxic cerebral damage and the resulting prognosis during the immediate postnatal period. Thus we aimed to determine whether the hypoxia-inducible transcription factors (HIF-1 and HIF-2) and/or their target genes in the placenta represent reliable indicators of hypoxic distress of the developing brain during systemic hypoxia at the end of gestation. To this end, pregnant mice were exposed to systemic hypoxia (inspired O2 fraction: 6%, 6 h) at gestational day 20. This hypoxic exposure significantly increased HIF-1α and HIF-2α protein levels in brain and placental tissue. Compared with normoxic controls, an increase of HIF-1α-immunoreactive neurons and HIF-2α-positive glial cells and vascular endothelial cells was observed in hypoxic cerebral cortex and hippocampus. In placenta, HIF-1α and HIF-2α were expressed in labyrinthine layer with increased staining intensity during hypoxia compared with normoxia. Significant upregulation of VEGF mRNA and protein in brain and placenta, as well as erythropoietin protein in placenta, indicated activity of the HIF system upon fetal hypoxia. Notably, hypoxia did not affect expression of the HIF target genes inducible nitric oxide synthase and GLUT-1. Taken together, at gestational day 20, systemic hypoxia led to upregulation of HIF-α in mouse brain that was temporally paralleled in placenta, implying that α-subunits of both HIF-1 and HIF-2 are indeed early markers of hypoxic distress in vivo. If our data reflect the situation in humans, analysis of the placenta will allow early identification of the hypoxic brain distress occurring near birth.
18
Alahari, Sruthi, Martin Post, Alessandro Rolfo, Rosanna Weksberg, and Isabella Caniggia. "Compromised JMJD6 Histone Demethylase Activity Affects VHL Gene Repression in Preeclampsia." Journal of Clinical Endocrinology & Metabolism 103, no. 4 (January 24, 2018): 1545–57. http://dx.doi.org/10.1210/jc.2017-02197.
Full textAbstract:
Abstract Context The von Hippel Lindau (VHL) protein is a key executor of the cellular hypoxic response that is compromised in preeclampsia, a serious disorder complicating 5% to 7% of pregnancies. To date, the mechanisms controlling VHL gene expression in the human placenta remain elusive. Objective We examined VHL epigenetic regulation in normal pregnancy and in preeclampsia, a pathology characterized by placental hypoxia. Design, Setting, and Participants Placentae were obtained from early-onset preeclampsia (n = 56; <34 weeks of gestation) and late-onset preeclampsia (n = 19; ≥34 weeks of gestation). Placentae from healthy normotensive age-matched preterm control (n = 43) and term control (n = 23) pregnancies were included as controls. Main Outcome Measure(s) We measured the activity of Jumonji domain containing protein 6 (JMJD6), a ferrous iron (Fe2+)– and oxygen-dependent histone demethylase, and examined its function in the epigenetic control of VHL. Results JMJD6 regulates VHL gene expression in the human placenta. VHL downregulation in preeclampsia is dependent on decreased JMJD6 demethylase activity due to hypoxia and reduced Fe2+ bioavailability. Chromatin immunoprecipitation assays revealed decreased association of JMJD6 and its histone targets with the VHL promoter. Findings in preeclampsia were corroborated in a murine model of pharmacological hypoxia using FG-4592. Placentae from FG-4592–treated mice exhibited reduced VHL levels, accompanied by placental morphological alterations and reduced pup weights. Notably, Fe2+ supplementation rescued JMJD6 histone demethylase activity in histone from E-PE and FG-4592–treated mice. Conclusions Our study uncovers epigenetic regulation of VHL and its functional consequences for altered oxygen and iron homeostasis in preeclampsia.
19
Stanek, Jerzy. "Utility of Diagnosing Various Histological Patterns of Diffuse Chronic Hypoxic Placental Injury." Pediatric and Developmental Pathology 15, no. 1 (January 2012): 13–23. http://dx.doi.org/10.2350/11-03-1000-oa.1.
Full textAbstract:
To examine the clinicopathologic correlations of three histological patterns of diffuse chronic hypoxic placental injury (preuterine [PR], uterine [UH], and postuterine [PU]), a retrospective statistical analysis of a large 14-year placental database was performed. Of 5097 placentas between 20 and 43 weeks of gestation examined consecutively, 4413 did not feature histological chronic placental hypoxia, while 684 did. In the latter, maternal hypertensive disorders, diabetes mellitus, abnormal cardiotocography and Dopplers, cesarean sections, inductions of labor, and fetal growth restriction, as well as other placental hypoxic lesions and decidual arteriolopathy, were statistically significantly more common than in the remaining placental material. Two hundred eighty-nine PR cases featured the most advanced gestational age and meconium staining; 237 UH cases featured severe preeclampsia, decidual arteriolopathy, villous infarction, membrane laminar necrosis, microscopic chorionic pseudocysts, excessive extravillous trophoblasts, and maternal floor multinucleate trophoblastic giant cells; and 158 PU cases featured the lowest placental weight and the highest prevalence of abnormal Dopplers, umbilical cord compromise, fetal growth restriction, cesarean section rate, and complicated 3rd stage of labor. The specificity of chronic hypoxic patterns of placental injury was much higher than the sensitivity, with the highest specificity for an excessive amount of extravillous trophoblasts. Diagnosing various hypoxic patterns of placental injury by histology may help to clarify the etiopathogenesis of a significant proportion of complications of pregnancy and abnormal fetal or neonatal outcomes. The patterns should help to retrospectively diagnose placental hypoxia, even in clinically unsuspected cases.
20
Kostyleva, Olga, Leila Stabayeva, Maida Tussupbekova, Irfan Mukhammad, Yevgeniy Kotov, Denis Kossitsyn, and S. N. Zhuravlev. "Erythroblasts in the Vessels of the Placenta – An Independent Factor of Chronic Hypoxic Damage to the Fetus." Open Access Macedonian Journal of Medical Sciences 10, A (March 21, 2022): 1151–56. http://dx.doi.org/10.3889/oamjms.2022.8745.
Full textAbstract:
The aim is a comparative histological study of the relative number of fetal erythroblasts in the vessels of the placentas from a full term pregnancy with a low and high risk of fetal hypoxic damage.
Material and methods. Based on data on the course of pregnancy, the state of health of the mother and the fetus/newborn, as well as histological examination of the placenta, 388 archived placenta tissue samples were selected in 2 groups: a high risk group for chronic hypoxic damage to the fetus and a group without clinical and laboratory signs of fetal/newborn hypoxia. The relationship between the number of erythroblasts in the vessels of the placenta and chronic hypoxic damage to the fetus was analyzed.
Results: The high risk of chronic hypoxic fetal damage is higher for placentas with ≥8 fetal erythroblasts in chorionic villi vessels (OR=3.175; 95% CI =1.921-5.248, p<0.001), with maternal vascular malperfusion (OR=2.798; 95% CI = 1.506-5.164, p=0.001) and combined (cross) placental lesions (OR=2.245; 95%CI=1.246-4.046, p =0.007) with damage of ≥30% of placental tissue.
Conclusion: 8 or more fetal erythroblasts in the lumen of the vessels of the placenta is an additional independent factor in chronic hypoxic damage to the fetus. These results are of practical importance for identifying a group of newborns with a high risk of chronic hypoxic damage in the perinatal period and stratification of the risk group in the postnatal period in order to reduce infant morbidity and mortality.
21
Zhang, Peilin. "Decidual Vasculopathy and Spiral Artery Remodeling Revisited III: Hypoxia and Re-oxygenation Sequence with Vascular Regeneration." Reproductive Medicine 1, no. 2 (July 11, 2020): 77–90. http://dx.doi.org/10.3390/reprodmed1020006.
Full textAbstract:
Aim: Spiral artery remodeling at early pregnancy is characterized by two distinct mechanisms with two morphologic features, namely, trophoblastic-dependent vascular invasion with “plugging”, and trophoblastic-independent mural muscular hypertrophy/hyperplasia, both of which lead to the blocking or narrowing of the arterial lumen with the consequence of reduced maternal blood flow to the developing embryo. Methods: Review of historic literature in light of the new discovery of CD56 (NCAM) expression on endovascular trophoblasts at late gestation, in relation to placental lateral growth with vascular regeneration. Results: Reduced maternal blood flow to the embryo results in a hypoxic condition critical for trophectoderm differentiation and proliferation. Hypoxia is also important for the development of hemangioblasts of vasculogenesis, and hematopoiesis of the placental villi. Up to 13 weeks, both uteroplacental and fetoplacental circulations are established and hypoxic condition relieved for normal fetal/placenta development by ultrasonography. The persistence of trophoblastic plugging and/or mural muscular hypertrophy/hyperplasia leads to persistent reduced maternal blood flow to the placenta, resulting in persistent hypoxia and increased angiogenesis, with a constellation of pathologic features of maternal vascular malperfusion atlate gestation. Wilm’s tumor gene (WT1) expression appears to be central to steroid and peptide hormonal actions in early pregnancy, and vascular regeneration/restoration after pregnancy. Conclusions: Spiral artery remodeling at early pregnancy leads to hypoxia with vascular transformation, and the establishment of uteroplacental circulation results in relief of hypoxia. The hypoxia–re-oxygenation sequence may provide insights into the mechanism of normal fetal/placental development and associated pregnancy complications, such as preeclampsia.
22
Tomlinson, Tracy M., Joel R. Garbow, Jeff R. Anderson, John A. Engelbach, D. Michael Nelson, and Yoel Sadovsky. "Magnetic resonance imaging of hypoxic injury to the murine placenta." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 2 (February 2010): R312—R319. http://dx.doi.org/10.1152/ajpregu.00425.2009.
Full textAbstract:
We assessed the use of magnetic resonance imaging (MRI) to define placental hypoxic injury associated with fetal growth restriction. On embryonic day 18.5 (E18.5) we utilized dynamic contrast-enhanced (DCE)-MRI on a 4.7-tesla small animal scanner to examine the uptake and distribution of gadolinium-based contrast agent. Quantitative DCE parameter analysis was performed for the placenta and fetal kidneys of three groups of pregnant C57BL/6 mice: 1) mice that were exposed to FiO2 = 12% between E15.5 and E18.5, 2) mice in normoxia with food restriction similar to the intake of hypoxic mice between E15.5 and E18.5, and 3) mice in normoxia that were fed ad libitum. After imaging, we assessed fetoplacental weight, placental histology, and gene expression. We found that dams exposed to hypoxia exhibited fetal growth restriction (weight reduction by 28% and 14%, respectively, P < 0.05) with an increased placental-to-fetal ratio. By using MRI-based assessment of placental contrast agent kinetics, referenced to maternal paraspinous muscle, we found decreased placental clearance of contrast media in hypoxic mice, compared with either control group (61%, P < 0.05). This was accompanied by diminished contrast accumulation in the hypoxic fetal kidneys (23%, P < 0.05), reflecting reduced transplacental gadolinium transport. These changes were associated with increased expression of placental Phlda2 and Gcm1 transcripts. Exposure to hypoxia near the end of mouse pregnancy reduces placental perfusion and clearance of contrast. MRI-based DCE imaging provides a novel tool for dynamic, in vivo assessment of placental function.
23
Vangrieken, Philippe, Salwan Al-Nasiry, Aalt Bast, Pieter A. Leermakers, Christy B. M. Tulen, Ger M. J. Janssen, Iris Kaminski, et al. "Hypoxia-induced mitochondrial abnormalities in cells of the placenta." PLOS ONE 16, no. 1 (January 12, 2021): e0245155. http://dx.doi.org/10.1371/journal.pone.0245155.
Full textAbstract:
Introduction Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown. Methods We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia. Furthermore, we explored the therapeutic potential of the antioxidants MitoQ and quercetin in preventing hypoxia-induced placental oxidative stress. Results Both in placental explants as well as BeWo cells, hypoxia resulted in reductions in mitochondrial content, decreased abundance of key molecules involved in the electron transport chain and increased expression and activity of glycolytic enzymes. Furthermore, expression levels of key regulators of mitochondrial biogenesis were decreased while the abundance of constituents of the mitophagy, autophagy and mitochondrial fission machinery was increased in response to hypoxia. In addition, placental hypoxia was associated with increased oxidative stress, inflammation, and apoptosis. Moreover, experiments with MitoQ revealed that hypoxia-induced reactive oxygen species originated from the mitochondria in the trophoblasts. Discussion This study is the first to demonstrate that placental hypoxia is associated with mitochondrial-generated reactive oxygen species and significant alterations in the molecular pathways controlling mitochondrial content and function. Furthermore, our data indicate that targeting mitochondrial oxidative stress may have therapeutic benefit in the management of pathologies related to placental hypoxia.
24
Nakashima, Akitoshi, Tomoko Shima, Sayaka Tsuda, Aiko Aoki, Mihoko Kawaguchi, Satoshi Yoneda, Akemi Yamaki-Ushijima, Shi-Bin Cheng, Surendra Sharma, and Shigeru Saito. "Disruption of Placental Homeostasis Leads to Preeclampsia." International Journal of Molecular Sciences 21, no. 9 (May 7, 2020): 3298. http://dx.doi.org/10.3390/ijms21093298.
Full textAbstract:
Placental homeostasis is directly linked to fetal well-being and normal fetal growth. Placentas are sensitive to various environmental stressors, including hypoxia, endoplasmic reticulum stress, and oxidative stress. Once placental homeostasis is disrupted, the placenta may rebel against the mother and fetus. Autophagy is an evolutionally conservative mechanism for the maintenance of cellular and organic homeostasis. Evidence suggests that autophagy plays a crucial role throughout pregnancy, including fertilization, placentation, and delivery in human and mouse models. This study reviews the available literature discussing the role of autophagy in preeclampsia.
25
Рудюк, Людмила Александровна, and Ольга Сергеевна Решетникова. "MORPHOLOGICAL CHARACTERISTICS OF VASCULAR-STROMAL REMODELING OF HUMAN PLACENTA VILLOUS CHORION IN CONDITIONS OF CIRCULATORY HYPOXIA." Морфология, no. 4-5 (September 30, 2020): 78–86. http://dx.doi.org/10.34922/ae.2020.158.4.012.
Full textAbstract:
Цель - изучение микроструктурных особенностей, ангиогенных и сосудисто-стромальных иммуногистохимических маркеров ремоделирования ворсин плаценты в условиях циркуляторной гипоксии различной степени тяжести. Материал и методы. Проведено гистологическое, иммуногистохимическое исследование тканей 54 плацент при доношенной беременности. Из них - 20 плацент - от женщин, у которых беременность протекала на фоне неоперированного врожденного порока сердца (ВПС); 19 плацент - при корригированном ВПС и 15 - при физиологическом течении беременности и родов (контроль). Во фрагментах плацентарной ткани проводили реакции с моноклональными мышиными антителами к VEGF, CD34, SMA, Collagen III, Collagen IV. Результаты. В работе представлены гистологическое строение ворсинчатого хориона при физиологически протекающей беременности, а также структурные особенности компенсаторно-приспособительных реакций плаценты в ответ на гипоксический стресс. Количественная оценка экспрессии сигнальных белковых молекул, участвующих в ремоделировании плацентарного барьера, выявила зависимость структурно-функциональной перестройки ворсин плаценты с учетом наличия гипоксемии у беременной женщины и степени ее выраженности. Установлены структурно-функциональные маркеры дезадаптации ворсинчатого хориона в условиях некорригированной циркулятоной гипоксемии, обусловленной ВПС. Отмечена активация компенсаторно-приспособительных процессов в плаценте при снижении гипоксемии у беременной с хирургической коррекцией порока сердца. Выводы. Компенсаторно-приспособительные процессы в плаценте, адекватный уровень репарации поврежденных плацентарных тканей являются необходимым условием физиологического течения беременности и родов. Нарушение процессов структурно-функционального ремоделирования ворсинчатого хориона в условиях циркуляторной гипоксии способствует развитию фетоплацентарной недостаточности, служит фактором риска перинатальной патологии плода и новорожденного. Адаптивная перестройка неоангиогенеза и экстрацеллюлярного матрикса ворсин плаценты способствует пролонгированию гестации, рождению живого, доношенного ребёнка. Objective - to study microstructural characteristics, angiogenic and vascular-stromal immunohistochemical markers of remodeling in the villous chorion of placenta in conditions of circulatory hypoxia of various severity levels. Material and methods. Histological and immunohistochemical study of the 54 term placentas was carried out. Twenty placentas were obtained from women suffering from non-operated CHD; 19 placentas - from women with corrected CHD and 15 - from women with normal pregnancy and delivery (controls). Monoclonal mouse antibodies raised against VEGF, CD34, SMA, Collagen III, and Collagen IV were used to carry out immunohistochemical reaction in specimens of placental tissue. Results. The paper demonstrated the histological structure of the chorionic villi obtained from women with normal pregnancy and structural characteristics of compensatory and adaptive response of placenta to hypoxic stress. The quantitative assessment of the expression of signaling protein molecules involved in the remodeling of the placental barrier demonstrated that the structural and functional restructuring of placental villi depended on hypoxemia and its intensity in pregnant women. Markers of structural and functional deadaptation of the chorionic villi in conditions of uncorrected circulation hypoxia caused by CHD were established. The signs of placental compensatory-adaptive processes activation in cases of surgical correction of the heart defect before pregnancy were identified. Conclusions. The compensatory and adaptive processes in placenta and adequate level of reparation of damaged placental tissues are vital condition of physiological course of pregnancy and childbirth. The violation of structural and functional remodeling of villous chorion in conditions of circulatory hypoxia contributes to the development of placental insufficiency, increases the risk of perinatal pathology of the fetus and the newborn. Adaptive remodeling of neoangiogenesis and extracellular matrix of placental villi contributes to gestation prolonging and live full-time birth.
26
Jakoubek, Vít, Jana Bíbová, Jan Herget, and Václav Hampl. "Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat." American Journal of Physiology-Heart and Circulatory Physiology 294, no. 4 (April 2008): H1638—H1644. http://dx.doi.org/10.1152/ajpheart.01120.2007.
Full textAbstract:
An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevations in fetoplacental resistance, that this effect is not completely reversible by acute reoxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of the fetoplacental vasculature. We measured fetoplacental vascular resistance as well as acute vasoconstrictor reactivity in isolated perfused placentae from rats exposed to hypoxia (10% O2) during the last week of a 3-wk pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate toward higher pressure values (by ∼20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying the involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by ∼75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.
27
Cowden Dahl, Karen D., Benjamin H. Fryer, Fiona A. Mack, Veerle Compernolle, Emin Maltepe, David M. Adelman, Peter Carmeliet, and M. Celeste Simon. "Hypoxia-Inducible Factors 1α and 2α Regulate Trophoblast Differentiation." Molecular and Cellular Biology 25, no. 23 (December 1, 2005): 10479–91. http://dx.doi.org/10.1128/mcb.25.23.10479-10491.2005.
Full textAbstract:
ABSTRACT Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1α and HIF2α, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIFα and HIFβ (ARNT) subunits. Placentas from Arnt − / − and Hif1α − / − Hif2α −/− embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hifα, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, and cell fate decisions, demonstrating that O2 tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia.
28
Tissot van Patot, Martha C., Andrew J. Murray, Virginia Beckey, Tereza Cindrova-Davies, Jemma Johns, Lisa Zwerdlinger, Eric Jauniaux, Graham J. Burton, and Natalie J. Serkova. "Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 1 (January 2010): R166—R172. http://dx.doi.org/10.1152/ajpregu.00383.2009.
Full textAbstract:
We have previously demonstrated placentas from laboring deliveries at high altitude have lower binding of hypoxia-inducible transcription factor (HIF) to DNA than those from low altitude. It has recently been reported that labor causes oxidative stress in placentas, likely due to ischemic hypoxic insult. We hypothesized that placentas of high-altitude residents acquired resistance, in the course of their development, to oxidative stress during labor. Full-thickness placental tissue biopsies were collected from laboring vaginal and nonlaboring cesarean-section term (37–41 wk) deliveries from healthy pregnancies at sea level and at 3,100 m. After freezing in liquid nitrogen within 5 min of delivery, we quantified hydrophilic and lipid metabolites using 31P and 1H NMR metabolomics. Metabolic markers of oxidative stress, increased glycolysis, and free amino acids were present in placentas following labor at sea level, but not at 3,100 m. In contrast, at 3,100 m, the placentas were characterized by the presence of concentrations of stored energy potential (phosphocreatine), antioxidants, and low free amino acid concentrations. Placentas from pregnancies at sea level subjected to labor display evidence of oxidative stress. However, laboring placentas at 3,100 m have little or no oxidative stress at the time of delivery, suggesting greater resistance to ischemia-reperfusion. We postulate that hypoxic preconditioning might occur in placentas that develop at high altitude.
29
Abdelghany Hassan Abdelghany, Ahmed Abdelghany Hassan, Sarah Abdelghany Hassan, and Rania Mohamed Fawzy. "Ultrastructural changes of the placenta in cases of preeclampsia." Magna Scientia Advanced Research and Reviews 3, no. 2 (November 30, 2021): 047–60. http://dx.doi.org/10.30574/msarr.2021.3.2.0080.
Full textAbstract:
The placenta plays vital roles during fetal development and growth. The ultrastructure of the placenta together with remodeling of the uterine spiral arteries are very important to maintain the utero-placental blood flow. Preeclampsia (PE) is a multifactorial disorder with abnormal placentation affecting the mother and fetus. The aim of this study was to study the ultrastructural abnormalities of the placenta in cases of PE. The placentas of 10 PE women and 10 controls were studied. Women of PE group were delivered by caesarian section while seven control women were delivered vaginally, and three by caesarian section. Placental samples were studied both morphologically and histologically by light and transmission electron microscopy. Light microscopic study of control placentas showed numerous microvilli, few syncytial knots, thin-walled blood vessels. PE placentas showed reduced number of microvilli with numerous syncytial knots, thick-walled vessels, edematous spaces, fibrotic areas and fibrinoid degeneration. Electron microscopic study of the control placentas showed a thick layer of syncytiotrophoblast (Sy), numerous microvilli and a thin layer of cytotrophoblast (Cy). PE placenta showed hypertrophy of Cy with atrophy of Sy and scarce microvilli. The trophoblast showed edematous vacuoles and glycogen storage areas. The villous core had congested capillaries, edematous spaces, glycogen storage areas and widespread areas of fibrosis. All the changes in PE placentas were attributed to hypoxia and oxidative stress and reduced utero-placental flow due to abnormal remodeling of the uterine spiral arteries that was aggravated by the thick placental barrier and the presence of edema, fibrosis and glycogen storage areas.
30
Stanek, Jerzy. "Chorangiosis of Chorionic Villi: What Does It Really Mean?" Archives of Pathology & Laboratory Medicine 140, no. 6 (June 1, 2016): 588–93. http://dx.doi.org/10.5858/arpa.2015-0160-oa.
Full textAbstract:
Chorangiosis has been regarded as a result of low-grade placental hypoxia associated with pregnancy risk factors and abnormal outcomes. It is unknown whether these are a consequence of chorangiosis itself or of associated other placental pathology.Context.— To prove that chorangiosis itself does not portend an increased risk for pregnancy unless associated with other placental pathology.Objective.— This retrospective statistical study analyzes 1231 consecutive placentas with diffuse or focal hypervascularity of chorionic villi: 328 with preuterine pattern of chronic hypoxic placental injury (group 1), 297 with uterine type of chronic hypoxic placental injury (group 2), and 606 cases with chorangiosis (group 3) not fulfilling the inclusion criteria for groups 1 or 2.Design.— Group 2, with 33 cases of chorangiosis (11.1%), featured 10 and 11 statistically significant highest percentages of abnormal clinical and placental variables, respectively; group 3 featured the highest percentages of multiple pregnancy, the heaviest placentas, and the most common acute chorioamnionitis, fetal inflammatory response; and group 1 had the highest proportion of mild erythroblastosis of fetal blood. When comparing groups 1 and 3, 21 of 29 clinical risk factors/outcomes (72.4%) and 30 of 41 placental variables (73.2%) were more common in group 1.Results.— Presence of diffuse hypoxic patterns of placental injury adds prognostically negative significance to increased vascularity of chorionic villi. Chorangiosis without those patterns portends minimal risk for the pregnancy, and is associated with significantly fewer pregnancy risk factors, abnormal outcomes, and other placental abnormalities.Conclusions.—
31
Ma, Rong, Yang Gu, Shuang Zhao, Jingxia Sun, Lynn J. Groome, and Yuping Wang. "Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies." American Journal of Physiology-Endocrinology and Metabolism 303, no. 7 (October 1, 2012): E928—E935. http://dx.doi.org/10.1152/ajpendo.00279.2012.
Full textAbstract:
Vitamin D insufficiency/deficiency during pregnancy has been linked to increased risk of preeclampsia. Placenta dysfunction plays an important role in the pathogenesis of this pregnancy disorder. In this study, we tested the hypothesis that disturbed vitamin D metabolism takes place in preeclamptic placentas. Protein expressions of vitamin D binding protein (VDBP), 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D receptor (VDR) were examined in placentas from normotensive and preeclamptic pregnancies. By immunostaining we found that in normal placenta VDBP, CYP24A1, and VDR expressions are localized mainly in trophoblasts, whereas CYP2R1 and CYP27B1 expressions are localized mainly in villous core fetal vessel endothelium. Protein expressions of CYP2R1 and VDR are reduced, but CYP27B1 and CYP24A1 expressions are elevated, in preeclamptic compared with normotensive placentas. Because increased oxidative stress is an underlying pathophysiology in placental trophoblasts in preeclampsia, we further determined whether oxidative stress contributes to altered vitamin D metabolic system in placental trophoblasts. Trophoblasts isolated from normal-term placentas were treated with hypoxic-inducing agent CoCl2, and protein expressions of VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR were determined. We found that hypoxia-induced downregulation of VDBP, CYP2R1, and VDR and upregulation of CYP27B1 and CYP24A1 expressions were consistent with that seen in preeclamptic placentas. CuZnSOD expression was also downregulated in trophoblasts treated with CoCl2. These results provide direct evidence of disrupted vitamin D metabolic homeostasis in the preeclamptic placenta and suggest that increased oxidative stress could be a causative factor of altered vitamin D metabolism in preeclamptic placentas.
32
Zhang, Meng-Ling, Qian Yang, Yan-Di Zhu, Ya-Di Zhang, Rui Zhang, Jian Liu, Xiao-Yan Zhao, et al. "Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway." Nutrients 14, no. 11 (June 1, 2022): 2332. http://dx.doi.org/10.3390/nu14112332.
Full textAbstract:
In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague–Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.
33
Armistead, Brooke, Leena Kadam, Sascha Drewlo, and Hamid-Reza Kohan-Ghadr. "The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight." International Journal of Molecular Sciences 21, no. 5 (March 5, 2020): 1775. http://dx.doi.org/10.3390/ijms21051775.
Full textAbstract:
The NFκB protein family regulates numerous pathways within the cell—including inflammation, hypoxia, angiogenesis and oxidative stress—all of which are implicated in placental development. The placenta is a critical organ that develops during pregnancy that primarily functions to supply and transport the nutrients required for fetal growth and development. Abnormal placental development can be observed in numerous disorders during pregnancy, including fetal growth restriction, miscarriage, and preeclampsia (PE). NFκB is highly expressed in the placentas of women with PE, however its contributions to the syndrome are not fully understood. In this review we discuss the molecular actions and related pathways of NFκB in the placenta and highlight areas of research that need attention
34
Boeuf, Philippe, Aimee Tan, Cleofe Romagosa, Jane Radford, Victor Mwapasa, Malcolm E. Molyneux, Steven R. Meshnick, Nicholas H. Hunt, and Stephen J. Rogerson. "Placental Hypoxia during Placental Malaria." Journal of Infectious Diseases 197, no. 5 (March 2008): 757–65. http://dx.doi.org/10.1086/526521.
Full text
35
Nevo, Ori, Nima Soleymanlou, Yuan Wu, Jing Xu, John Kingdom, Ariel Many, Stacy Zamudio, and Isabella Caniggia. "Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 4 (October 2006): R1085—R1093. http://dx.doi.org/10.1152/ajpregu.00794.2005.
Full textAbstract:
Elevated expression of soluble vascular endothelial growth factor receptor-1 (sFlt-1) in preeclampsia plays a major role in the pathogenesis of this serious disorder of human pregnancy. Although reduced placental oxygenation is thought to be involved in the pathogenesis of preeclampsia, it is unclear how oxygen regulates placental sFlt-1 expression. The aims herein were to investigate sFlt-1 expression in in vivo and in vitro physiological and pathological models of human placental hypoxia and to understand the role of hypoxia inducible factor-1 (HIF-1) in regulating the expression of this molecule. sFlt-1 expression in placental villi was significantly increased under physiological low oxygen conditions in early first-trimester and in high-altitude placentae, as well as in pathological low oxygen conditions, such as preeclampsia. In high-altitude and in preeclamptic tissue, sFlt-1 localized within villi to perivascular regions, the syncytiotrophoblast layer, and syncytial knots. In first-trimester villous explants, low oxygen, but not hypoxia-reoxygenation (HR), increased sFlt-1 expression. Moreover, exposure of villous explants to dimethyloxalyl-glycin, a pharmacological inhibitor of prolyl-hydroxylases, which mimics hypoxia by increasing HIF-1α stability, increased sFlt-1 expression. Conversely, HIF-1α knockdown using antisense oligonucleotides, decreased sFlt-1 expression. In conclusion, placental sFlt-1 expression is increased by both physiologically and pathologically low levels of oxygen. This oxygen-induced effect is mediated via the transcription factor HIF-1. Low oxygen levels, as opposed to intermittent oxygen tension (HR) changes, play an important role in regulating sFlt-1 expression in the developing human placenta and hence may contribute to the development of preeclampsia.
36
Matskevich, Natallia V., and Marina P. Famina. "Integrated 2D Doppler indices of uteroplacental and fetal blood flow in diagnosis of intrauterine hypoxia." RUDN Journal of Medicine 25, no. 4 (December 17, 2021): 290–97. http://dx.doi.org/10.22363/2313-0245-2021-25-4-290-297.
Full textAbstract:
Relevance . Intrauterine hypoxia associated with placental disorders is a significant factor of ante-, intra- and postnatal fetal and newborn death. Despite clinical examination of pregnant women using ultrasound and cardiotocography, cases of intrauterine hypoxia often remain undetected prenatally. Clinical manifestation of placental disorders and intrauterine hypoxia are associated with pathological changes of blood flow resistance in the uterine, placental and fetal vessels. A combined Doppler assessment of blood flow in the uterine, placental and fetal vessels could improve detection of intrauterine hypoxia. The aim of the study was to assess the prognostic significance of integrated 2D Doppler indices of uteroplacental and fetal blood flow for the detection of fetal hypoxia in the 3rd trimester and to predict unfavorable perinatal outcomes. Materials and Methods. The outcomes of pregnancy of 48 women with fetal hypoxia delivered at 29 - 40 gestational weeks (study group), and 21 women who gave birth to healthy full-term infants (control group) were retrospectively analyzed. On the eve of delivery all women had 2D Doppler assessment of the uterine arteries, umbilical arteries, and fetal middle cerebral artery with an assessment of the cerebro-placental ratio, umbilical-cerebral ratio and cerebro-placental-uterine ratio. Results and Discussion . Analysis of the obtained values of cerebro-placental-uterine ratio, cerebro-placental ratio and umbilical-cerebral ratio showed the benefit from use of integrated 2D Doppler indices in the diagnosis of fetal hypoxia at 29 - 40 gestations weeks and in predicting complications in newborns. The high sensitivity of the cerebro-placental-uterine ratio (90.5%) makes it possible to effectively use this index for the diagnosis of intrauterine hypoxia. Conclusion. Pathological cerebro-placental-uterine ratio 2.44 is a clinically significant 2D Doppler criterion that predicts a high risk of asphyxia, respiratory distress syndrome, hypotrophy, and perinatal hypoxic-ischemic encephalopathy. Lower values of the cerebro-placental ratio and umbilical-cerebral ratio sensitivity (77.1% and 81.3%, respectively) limit their use for the diagnosis of fetal hypoxia as compared with cerebro-placental-uterine ratio.
37
Anggraini, Nutria Widya Purna, Sri Sulistyowati, Muhammad Adrianes Bachnas, Eric Edwin Yuliantara, Wisnu Prabowo, and Uki Retno Budihastuti. "Hypoxia Inducible Factor-1-Alpha Expression on Preeclampsia Mice Model With L-Arginine Administration." Folia Medica Indonesiana 57, no. 3 (September 5, 2021): 226. http://dx.doi.org/10.20473/fmi.v57i3.22733.
Full textAbstract:
Preeclampsia is hypertension in pregnancy that affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. In the pathogenesis of preeclampsia, placental hypoxia plays an important role, associated with excessive trophoblast apoptosis resulting in decreased trophoblast and spiral arteries invasion. This placental hypoxic condition will induce increased expression of Hypoxia Inducible Factor -1-Alpha (HIF-1-A). L-Arginine is a potent vasodilator presumably to improve preeclampsia placental hypoxic conditions and reduce HIF-1-A expression. This study was an experimental study with a parallel-group post-test only design. Thirty-six preeclamptic mice models were divided into 2 groups. The control group (K1) 18 preeclamptic mice model without treatment and the treatment group (K2) 18 preeclamptic mice given L-Arginine. The independent variable was the administration of L-Arginine and the dependent variable is the placental HIF-1-A expression. Statistical analysis used unpaired t-test on normal data distribution, and Mann Whitney test on abnormal data distribution. The mean of placental HIF-1-A expression K1 was 2.47 ± 1.65 with a minimum value of 0.4 and a maximum value of 6.6. At K2 0.93 ± 0.55 with a minimum value of 0.0 and a maximum value of 2.0. Statistical tests showed that the placental HIF-1-A expression in the treatment group was significantly lower than that in the control group (p <0.001). In conclusion, the expression of HIF-1-A in preeclamptic mice model placenta decreased with L-Arginine administration.
38
Kusinski, Laura C., Joanna L. Stanley, Mark R. Dilworth, Cassandra J. Hirt, Irene J. Andersson, Lewis J. Renshall, Bernadette C. Baker, et al. "eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 303, no. 1 (July 1, 2012): R86—R93. http://dx.doi.org/10.1152/ajpregu.00600.2011.
Full textAbstract:
Fetal growth restriction (FGR) is the inability of a fetus to reach its genetically predetermined growth potential. In the absence of a genetic anomaly or maternal undernutrition, FGR is attributable to “placental insufficiency”: inappropriate maternal/fetal blood flow, reduced nutrient transport or morphological abnormalities of the placenta (e.g., altered barrier thickness). It is not known whether these diverse factors act singly, or in combination, having additive effects that may lead to greater FGR severity. We suggest that multiplicity of such dysfunction might underlie the diverse FGR phenotypes seen in humans. Pregnant endothelial nitric oxide synthase knockout (eNOS−/−) dams exhibit dysregulated vascular adaptations to pregnancy, and eNOS−/− fetuses of such dams display FGR. We investigated the hypothesis that both altered vascular function and placental nutrient transport contribute to the FGR phenotype. eNOS−/− dams were hypertensive prior to and during pregnancy and at embryonic day (E) 18.5 were proteinuric. Isolated uterine artery constriction was significantly increased, and endothelium-dependent relaxation significantly reduced, compared with wild-type (WT) mice. eNOS−/− fetal weight and abdominal circumference were significantly reduced compared with WT. Unidirectional maternofetal 14C-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent 14C-MeAIB uptake into mouse placental vesicles were both significantly lower in eNOS−/− fetuses, indicating diminished placental nutrient transport. eNOS−/− mouse placentas demonstrated increased hypoxia at E17.5, with elevated superoxide compared with WT. We propose that aberrant uterine artery reactivity in eNOS−/− mice promotes placental hypoxia with free radical formation, reducing placental nutrient transport capacity and fetal growth. We further postulate that this mouse model demonstrates “uteroplacental hypoxia,” providing a new framework for understanding the etiology of FGR in human pregnancy.
39
Sosnina, Aleksandra K., Tatyana G. Tral, and Julia S. Krylova. "Functional morphology of the placental villous tree at term singleton pregnancies, achieved by methods of assisted reproductive technology." Journal of obstetrics and women's diseases 65, no. 3 (June 15, 2016): 43–51. http://dx.doi.org/10.17816/jowd65343-51.
Full textAbstract:
Introduction. Of special interest in the use of assisted reproductive technology techniques (ART) is the placenta as the main authority responsible for the formation and growth of the fetus. Purpose and objectives. The aim of our research is to study the morpho-functional state of placenta after pregnancy achieved by means of ART. Research objectives: histological and immunohistochemical study using the CD34, NOS-3 and HIF in these placentas. Methods. Total 98 placentas from full-term singleton pregnancies with gestational age were examined. Two study groups were formed: a basic group - the placenta from pregnancy induced methods of ART (n = 60) was divided into I subgroup, which included 30 placentas from women with primary infertility and II subgroup - 30 placentas from women with secondary infertility comparison group consisted of the placenta from the naturally ensuing pregnancy (12 placentas from primigravidae and 26 placentas from multiparous patients). Results. Histological examination of the morphological structure of the placenta was found that the incidence of chronic placental insufficiency was 1.4 times higher than in the subgroup with secondary infertility. Immunohistochemical study of placentas in the basic group, there was a significant decrease in the expression of cell adhesion marker (CD34) in the vascular epithelium chorionic villi, decreased expression of vascular tone marker (NOS-3) and increase the expression of hypoxia-inducible factor (HIF-1α) in the basic group compared to placenta s from children born naturally. Changes in the expression of the studied markers are most pronounced in the placentas from children born with secondary infertility, which is likely due to the high incidence of inflammatory diseases of the pelvic organs in this subgroup. Conclusions. Endometrial pathology in primary and secondary infertility, can cause the formation of functional disorders and morphological structure of placental complex and occurrence in the future placental insufficiency.
40
Cvitic, Silvija, Gernot Desoye, and Ursula Hiden. "Glucose, Insulin, and Oxygen Interplay in Placental Hypervascularisation in Diabetes Mellitus." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/145846.
Full textAbstract:
The placental vasculature rapidly expands during the course of pregnancy in order to sustain the growing needs of the fetus. Angiogenesis and vascular growth are stimulated and regulated by a variety of growth factors expressed in the placenta or present in the fetal circulation. Like in tumors, hypoxia is a major regulator of angiogenesis because of its ability to stimulate expression of various proangiogenic factors. Chronic fetal hypoxia is often found in pregnancies complicated by maternal diabetes as a result of fetal hyperglycaemia and hyperinsulinemia. Both are associated with altered levels of hormones, growth factors, and proinflammatory cytokines, which may act in a proangiogenic manner and, hence, affect placental angiogenesis and vascular development. Indeed, the placenta in diabetes is characterized by hypervascularisation, demonstrating high placental plasticity in response to diabetic metabolic derangements. This review describes the major regulators of placental angiogenesis and how the diabetic environmentin uteroalters their expression. In the light of hypervascularized diabetic placenta, the focus was placed on proangiogenic factors.
41
Ekawati, Maria, Ninik Mujihartini, Ahmad A. Jusuf, Nani Dharmasetiawani, Sri W. A. Jusman, and Mohamad Sadikin. "Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage." Medical Journal of Indonesia 25, no. 3 (October 14, 2016): 143–50. http://dx.doi.org/10.13181/mji.v25i3.1287.
Full textAbstract:
Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of intraventricular hemorrhage in premature infants.Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic). Hypoxia inducible factor (HIF)-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA) and glutathione (GSH) served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH) was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data.Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61), respectively} compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31)}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91) and 38.47(ranged 16.49–126.76) ng/mg protein, respectively. mRNA expression of N-cadherin (0.13) and occludin (0.096) were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001), while protein expression of N-cadherin (3.4; 75.9; 6.9; 13.8%) and occludin (20.7; 3.4; 69.0; 3.4; 6.9%) in hypoxia group was not associated with IVH (p=0.783 and p=0.743).Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.
42
Liong, Stella, Gillian Barker, and Martha Lappas. "Bromodomain protein BRD4 is increased in human placentas from women with early-onset preeclampsia." Reproduction 155, no. 6 (June 2018): 573–82. http://dx.doi.org/10.1530/rep-17-0744.
Full textAbstract:
Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma. The aims of this study were to: (i) determine the effect of severe early-onset preeclampsia on placental BRD4 expression; (ii) the effect of loss of BRD4 function by siRNA-targeted knockdown or with the BRD inhibitor JQ1 in human primary trophoblast cells and human umbilical vein endothelial cells (HUVECs) on TNF-stimulated production of pro-inflammatory mediators, cell adhesion molecules and anti-angiogenic markers and (iii) the effect of BRD4 suppression on placental sFLT1 secretion under hypoxia conditions and in preeclampic placenta. BRD4 mRNA expression was significantly increased (sevenfold) in severe early-onset preeclampsia placenta. BRD4 silencing resulted in a significant reduction in TNF-induced IL6, CXCL8, CCL2, CXCL1 and sFLT1-e15a mRNA expression and IL6, CXCL8, CCL2, CXCL1 and sFLT1 secretion in primary trophoblast and HUVECs. Additionally, JQ1 treatment significantly reduced placental sFLT1 secretion under hypoxic conditions and in preterm preeclamptic placenta. In conclusion, these findings suggest BRD4 may play a central role in propagating inflammation and endothelial dysfunction associated with the pathophysiology of early-onset preeclampsia.
43
Kreis, Nina-Naomi, Alexandra Friemel, Lukas Jennewein, Samira Catharina Hoock, Anna Elisabeth Hentrich, Thorsten Nowak, Frank Louwen, and Juping Yuan. "Functional Analysis of p21Cip1/CDKN1A and Its Family Members in Trophoblastic Cells of the Placenta and Its Roles in Preeclampsia." Cells 10, no. 9 (August 27, 2021): 2214. http://dx.doi.org/10.3390/cells10092214.
Full textAbstract:
Preeclampsia (PE), a gestational hypertensive disease originating from the placenta, is characterized by an imbalance of various cellular processes. The cell cycle regulator p21Cip1/CDKN1A (p21) and its family members p27 and p57 regulate signaling pathways fundamental to placental development. The aim of the present study was to enlighten the individual roles of these cell cycle regulators in placental development and their molecular involvement in the pathogenesis of PE. The expression and localization of p21, phospho-p21 (Thr-145), p27, and p57 was immunohistochemically analyzed in placental tissues from patients with early-onset PE, early-onset PE complicated by the HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome as well as late-onset PE compared to their corresponding control tissues from well-matched women undergoing caesarean sections. The gene level was evaluated using real-time quantitative PCR. We demonstrate that the delivery mode strongly influenced placental gene expression, especially for CDKN1A (p21) and CDKN1B (p27), which were significantly upregulated in response to labor. Cell cycle regulators were highly expressed in first trimester placentas and impacted by hypoxic conditions. In support of these observations, p21 protein was abundant in trophoblast organoids and hypoxia reduced its gene expression. Microarray analysis of the trophoblastic BeWo cell line depleted of p21 revealed various interesting candidate genes and signaling pathways for the fusion process. The level of p21 was reduced in fusing cytotrophoblasts in early-onset PE placentas and depletion of p21 led to reduced expression of fusion-related genes such as syncytin-2 and human chorionic gonadotropin (β-hCG), which adversely affected the fusion capability of trophoblastic cells. These data highlight that cell cycle regulators are important for the development of the placenta. Interfering with p21 influences multiple pathways related to the pathogenesis of PE.
44
Rudyuk, L. A., and O. S. Reshetnikova. "Congenital heart defects and pregnancy: current view on the mechanisms of placental adaptation to circulatory hypoxia." Voprosy ginekologii, akušerstva i perinatologii 19, no. 6 (2020): 70–82. http://dx.doi.org/10.20953/1726-1678-2020-6-70-82.
Full textAbstract:
In this review, we perform clinical and morphological analysis of the mechanisms underlying adaptation of the human placenta to hypoxia in the fetoplacental complex in pregnant women with congenital heart defects (CHDs). We assessed specific characteristics of macroscopic and microscopic structure of the placenta in women with this extragenital pathology. We descried morphological involutive dystrophic and compensatory mechanisms that develop in the placenta of women with impaired hemodynamics. We proposed molecular markers, whose investigation will clarify functional state of the placental barrier and ways of remodeling vascular-stromal components of the villous chorion. Potential risks associated with circulatory hypoxia in the mother-placenta-fetus system should be taken into account in the management of pregnant women with CHDs. Detection of placental maladaptation signs in mothers with CHDs will help to identify the risk group of newborns, organize preventive therapy, prophylaxis of diseases, health improvement, and treatment of newborns. Key words: compensatory and adaptive processes, hypoxia, immunohistochemistry, morphology, placenta
45
Kedziora, Sarah M., Benedikt Obermayer, Meryam Sugulle, Florian Herse, Kristin Kräker, Nadine Haase, Immaculate M. Langmia, et al. "Placental Transcriptome Profiling in Subtypes of Diabetic Pregnancies Is Strongly Confounded by Fetal Sex." International Journal of Molecular Sciences 23, no. 23 (December 6, 2022): 15388. http://dx.doi.org/10.3390/ijms232315388.
Full textAbstract:
The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio–temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ.
46
Murphy, Ciara N., Susan P. Walker, Teresa M. MacDonald, Emerson Keenan, Natalie J. Hannan, Mary E. Wlodek, Jenny Myers, et al. "Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction." International Journal of Molecular Sciences 22, no. 14 (July 12, 2021): 7467. http://dx.doi.org/10.3390/ijms22147467.
Full textAbstract:
Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (<34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency.
47
Srinivasan, Anu Priyadharshini, B. O. Parijatham Omprakash, Kandhimalla Lavanya, Priyadharshini Subbulakshmi Murugesan, and Saraswathi Kandaswamy. "A Prospective Study of Villous Capillary Lesions in Complicated Pregnancies." Journal of Pregnancy 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/193925.
Full textAbstract:
The vascularity of placental tissue is dependent on various factors of which fetomaternal hypoxia plays a major role. Hypoxia can be of different types and each type influences the vascularity of the villi, especially terminal villi, in its own way. In this study, we attempted to identify villous vascular changes in a group of term placentae from mothers with diseases complicating pregnancy. Chorangiosis was the most frequently identified lesion while chorangioma was found in only 2 cases. There were no cases of chorangiomatosis. A few cases had normal villous vasculature. Maternal diseases have a major role in disrupting the placental vasculogenesis and angiogenesis by creating a hypoxic environment that may affect the fetus adversely. Hence, such conditions need to be identified early in pregnancy and managed appropriately as it is possible to maintain a normal vasculature and prevent neonatal mortality and morbidity if prompt intervention is done.
48
Masoumi, Zahra, Lena Erlandsson, Eva Hansson, Mattias Magnusson, Eva Mezey, and Stefan R. Hansson. "Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas." International Journal of Molecular Sciences 22, no. 7 (March 25, 2021): 3357. http://dx.doi.org/10.3390/ijms22073357.
Full textAbstract:
Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. To investigate the role of the placenta in increasing globin levels previously reported in PE, flow cytometry, histological and immunostaining and in situ analyses were used on placenta samples and ex vivo explant cultures. Our results indicated that in PE pregnancies, placental HSPC homing and erythropoiesis were not affected. Non-erythroid alpha-globin mRNA and protein, but not gamma-globin, were detected in syncytiotrophoblasts and stroma of PE placenta samples. Similarly, alpha-globin protein and mRNA were upregulated in normal placenta explants cultured in hypoxia. The upregulation was independent of HIF1 and NRF2, the two main candidates of globin transcription in non-erythroid cells. Our study is the first to demonstrate alpha-globin mRNA expression in syncytiotrophoblasts in PE, induced by hypoxia. However, gamma-globin was only expressed in erythrocytes. We conclude that alpha-globin, but not HbF, is expressed in placental syncytiotrophoblasts in PE and may contribute to the pathology of the disease.
49
León, José, Jesenia Acurio, Lina Bergman, Juán López, Anna Karin Wikström, Pablo Torres-Vergara, Felipe Troncoso, Fidel Ovidio Castro, Manu Vatish, and Carlos Escudero. "Disruption of the Blood-Brain Barrier by Extracellular Vesicles From Preeclampsia Plasma and Hypoxic Placentae: Attenuation by Magnesium Sulfate." Hypertension 78, no. 5 (November 2021): 1423–33. http://dx.doi.org/10.1161/hypertensionaha.121.17744.
Full textAbstract:
Preeclampsia, a pregnancy-related endothelial disorder, is associated with both cardiovascular and cerebrovascular complications. Preeclampsia requires the presence of a placenta as part of its pathophysiology, yet the role of this organ in the cerebrovascular complications remains unclear. Research has shown that circulating small extracellular vesicles (also known as exosomes) present in preeclampsia plasma can generate endothelial dysfunction, but it is unclear whether the impairment of function of brain endothelial cells at the blood-brain barrier is secondary to plasma-derived or placental-derived exosomes. In this study, we evaluated the effect of small extracellular vesicles isolated from plasma samples of women with preeclampsia (n=12) and women with normal pregnancy (n=11) as well as from human placental explants from normotensive pregnancies (n=6) subjected to hypoxia (1% oxygen) on the integrity of the blood-brain barrier, using both in vitro and animal models. Exposure of human-derived brain endothelial cell monolayers to plasma and plasma-derived small extracellular vesicles from preeclamptic pregnancies increased the permeability and reduced the transendothelial electrical resistance. A similar outcome was observed with hypoxic placental-derived small extracellular vesicles, which also increased the permeability to Evan’s blue in the brain of C57BL6 nonpregnant mice. Cotreatment with magnesium sulfate reversed the effects elicited by plasma, plasma-derived, and hypoxic placental-derived small extracellular vesicles in the employed models. Thus, circulating small extracellular vesicles in plasma from women with preeclampsia or from hypoxic placentae disrupt the blood-brain barrier, which can be prevented using magnesium sulfate. These findings provide new insights into the pathophysiology of cerebral complications associated with preeclampsia.
50
Chakraborty, Damayanti, Wei Cui, Gracy X. Rosario, Regan L. Scott, Pramod Dhakal, Stephen J. Renaud, Makoto Tachibana, et al. "HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia." Proceedings of the National Academy of Sciences 113, no. 46 (November 2, 2016): E7212—E7221. http://dx.doi.org/10.1073/pnas.1612626113.
Full textAbstract:
The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. Hypoxia plays an instructive role in influencing trophoblast cell differentiation and regulating placental organization. Key downstream hypoxia-activated events were delineated using rat TS cells and tested in vivo, using trophoblast-specific lentiviral gene delivery and genome editing. DNA microarray analyses performed on rat TS cells exposed to ambient or low oxygen and pregnant rats exposed to ambient or hypoxic conditions showed up-regulation of genes characteristic of an invasive/vascular remodeling/inflammatory phenotype. Among the shared up-regulated genes was matrix metallopeptidase 12 (MMP12). To explore the functional importance of MMP12 in trophoblast cell-directed spiral artery remodeling, we generated an Mmp12 mutant rat model using transcription activator-like nucleases-mediated genome editing. Homozygous mutant placentation sites showed decreased hypoxia-dependent endovascular trophoblast invasion and impaired trophoblast-directed spiral artery remodeling. A link was established between hypoxia/HIF and MMP12; however, evidence did not support Mmp12 as a direct target of HIF action. Lysine demethylase 3A (KDM3A) was identified as mediator of hypoxia/HIF regulation of Mmp12. Knockdown of KDM3A in rat TS cells inhibited the expression of a subset of the hypoxia–hypoxia inducible factor (HIF)-dependent transcripts, including Mmp12, altered H3K9 methylation status, and decreased hypoxia-induced trophoblast cell invasion in vitro and in vivo. The hypoxia-HIF-KDM3A-MMP12 regulatory circuit is conserved and facilitates placental adaptations to environmental challenges.