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1
Taher, Shèdy, Yamilette Borja, Lucía Cabanela, Vincent J. Costers, Morgan Carson-Marino, Julie C. Bailes, Biswadeep Dhar, et al. "Cholecystokinin, gastrin, cholecystokinin/gastrin receptors, and bitter taste receptor TAS2R14: trophoblast expression and signaling." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 316, no. 5 (May 1, 2019): R628—R639. http://dx.doi.org/10.1152/ajpregu.00153.2018.
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We investigated expression of cholecystokinin (CCK) in humans and mice, and the bitter taste receptor TAS2R14 in the human placenta. Because CCK and gastrin activate the CCKBR receptor, we also explored placental gastrin expression. Finally, we investigated calcium signaling by CCK and TAS2R14. By RT-PCR, we found CCK/Cck and GAST/Gast mRNA expression in both normal human and mouse placentas, as well as in human trophoblast cell lines (TCL). Although both Cckar and – br mRNA were expressed in the mouse placenta, only CCKBR mRNA was detected in the human placenta and TCL. mRNA expression for TAS2R14 was also observed in the human placenta and TCL. Using immunohistochemistry, CCK protein was localized to the syncytiotrophoblast (ST) and extravillous trophoblast (EVT) in the human term placenta, and to trophoblast glycogen cells in mouse and human placentas. Gastrin and TAS2R14 proteins were also observed in ST and EVT of the human placenta. Both sulfated and nonsulfated CCK elicited a comparable rise in intracellular calcium in TCL, consistent with CCKBR expression. Three TAS2R14 agonists, flufenamic acid, chlorhexidine, and diphenhydramine, also evoked rises in intracellular calcium in TCL. These results establish CCK, gastrin, and their receptor(s) in both human and mouse placentas, and TAS2R14 in the human placenta. Both CCK and TAS2R14 agonists increased intracellular calcium in human TCL. Although the roles of these ligands and receptors, and their potential cross talk in normal and pathological placentas, are currently unknown, this study opens new avenues for placental research.
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Lien, Yu-Chin, Zhe Zhang, Yi Cheng, Erzsebet Polyak, Laura Sillers, Marni J. Falk, Harry Ischiropoulos, Samuel Parry, and Rebecca A. Simmons. "Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth." International Journal of Molecular Sciences 22, no. 15 (July 23, 2021): 7899. http://dx.doi.org/10.3390/ijms22157899.
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A well-functioning placenta is crucial for normal gestation and regulates the nutrient, gas, and waste exchanges between the maternal and fetal circulations and is an important endocrine organ producing hormones that regulate both the maternal and fetal physiologies during pregnancy. Placental insufficiency is implicated in spontaneous preterm birth (SPTB). We proposed that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may ultimately result in SPTB. To explore our hypothesis, we performed a RNA-seq study in male and female placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation) to assess the alterations in the gene expression profiles. We focused exclusively on Black women (cases and controls), who are at the highest risk of SPTB. Six hundred and seventy differentially expressed genes were identified in male SPTB placentas. Among them, 313 and 357 transcripts were increased and decreased, respectively. In contrast, only 61 differentially expressed genes were identified in female SPTB placenta. The ingenuity pathway analysis showed alterations in the genes and canonical pathways critical for regulating inflammation, oxidative stress, detoxification, mitochondrial function, energy metabolism, and the extracellular matrix. Many upstream regulators and master regulators important for nutrient-sensing and metabolism were also altered in SPTB placentas, including the PI3K complex, TGFB1/SMADs, SMARCA4, TP63, CDKN2A, BRCA1, and NFAT. The transcriptome was integrated with published human placental metabolome to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the transcriptome were identified in SPTB placentas with fetal sex disparities. Altered energy metabolism, mitochondrial function, inflammation, and detoxification may underly the mechanisms of placental dysfunction in SPTB.
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Osifo, E. O., and V. C. Ezeuko. "Histological Assessment of Placental Development Following Intrauterine Exposure to Caffeine in Adult Wistar Rats." Journal of Applied Sciences and Environmental Management 28, no. 4 (April 29, 2024): 1115–20. http://dx.doi.org/10.4314/jasem.v28i4.11.
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In recent years, there have been concerns about human reproductive disorders. Physiological adaptations are crucial for optimal fetal development during pregnancy. The widespread consumption of caffeine by pregnant women raises questions about its impact on maternal physiology and fetal development. Hence, the objective of this study was to evaluate the histological assessment of placenta development following intrauterine exposure to caffeine in adult Wistar rats using appropriate standard techniques. On each gestational day (GD13, GD15, GD17, and GD19), five (5) animals were sampled from each group and their placentas were harvested for histological assessment. The Maternal weight, Fetal Crown Rump Length, Placental weight, Placental diameter major, Placental diameter minor, and fetal weight were taken on the harvested placenta. Results showed varying alterations in the histomorphology of the placenta ranging from delayed differentiation of glycogen cells, dilated and congested blood vessels, vacuolar degeneration of glycogen cell islands, poor development of the labyrinth zone, and dilated fetal capillaries. In conclusion, there is histomorphological evidence that caffeine administration has deleterious effects on the development of the placenta in Wistar rats.
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Rampon, Christine, Stéphanie Bouillot, Adriana Climescu-Haulica, Marie-Hélène Prandini, Francine Cand, Yves Vandenbrouck, and Philippe Huber. "Protocadherin 12 deficiency alters morphogenesis and transcriptional profile of the placenta." Physiological Genomics 34, no. 2 (July 2008): 193–204. http://dx.doi.org/10.1152/physiolgenomics.00220.2007.
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Protocadherins are transmembrane proteins exhibiting homophilic adhesive activities through their extracellular domain. Protocadherin 12 ( Pcdh12) is expressed in angiogenic endothelial cells, mesangial cells of kidney glomeruli, and glycogen cells of the mouse placenta. To get insight into the role of this protein in vivo, we analyzed PCDH12-deficient mice and investigated their placental phenotype. The mice were alive and fertile; however, placental and embryonic sizes were reduced compared with wild-type mice. We observed defects in placental layer segregation and a decreased vascularization of the labyrinth associated with a reduction in cell density in this layer. To understand the molecular events responsible for the phenotypic alterations observed in Pcdh12−/− placentas, we analyzed the expression profile of embryonic day 12.5 mutant placentas compared with wild-type placentas, using pangenomic chips: 2,289 genes exhibited statistically significant changes in expressed levels due to loss of PCDH12. Functional grouping of modified genes was obtained by GoMiner software. Gene clusters that contained most of the differentially expressed genes were those involved in tissue morphogenesis and development, angiogenesis, cell-matrix adhesion and migration, immune response, and chromatin remodeling. Our data show that loss of PCDH12 leads to morphological alterations of the placenta and to notable changes in its gene expression profile. Specific genes emerging from the microarray screen support the biological modifications observed in PCDH12-deficient placentas.
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Selvaratnam, Johanna, Haiyan Guan, James Koropatnick, and Kaiping Yang. "Metallothionein-I- and -II-deficient mice display increased susceptibility to cadmium-induced fetal growth restriction." American Journal of Physiology-Endocrinology and Metabolism 305, no. 6 (September 15, 2013): E727—E735. http://dx.doi.org/10.1152/ajpendo.00157.2013.
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Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. The placenta is the main organ known to protect the fetus from environmental toxins such as cadmium. In this study, we examine the role of the two key placental factors in cadmium-induced FGR. The first is placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is known to protect the fetus from exposure to high cortisol levels and subsequently FGR, and the second the cadmium binding/sequestering proteins metallotheionein (MT)-I and -II. Using the MT-I/II −/− mouse model, pregnant mice were administered cadmium, following which pups and placentas were collected and examined. MT-I/II−/− pups exposed to cadmium were significantly growth restricted, but neither placental weight nor 11β-HSD2 was altered. Although cadmium administration did not result in any visible structural changes in the placenta, increased apoptosis was detected in MT-I/II−/− placentas following cadmium exposure, with a significant increase in levels of both p53 and caspase 3 proteins. Additionally, glucose transporter (GLUT1) was significantly reduced in MT-I/II−/− placentas of pups exposed to cadmium, whereas zinc transporter (ZnT-1) remained unaltered. Taken together, these results demonstrate that MT-I/II−/− mice are more vulnerable to cadmium-induced FGR. The present data also suggest that increased apoptosis and reduced GLUT1 expression in the placenta contribute to the molecular mechanisms underlying cadmium-induced FGR.
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Flores-Pliego, Arturo, Jael Miranda, Sara Vega-Torreblanca, Yolotzin Valdespino-Vázquez, Cecilia Helguera-Repetto, Aurora Espejel-Nuñez, Héctor Borboa-Olivares, et al. "Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19." Cells 10, no. 2 (February 10, 2021): 364. http://dx.doi.org/10.3390/cells10020364.
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Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.
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Vaughan, Owen R., Fredrick Thompson, Ramón A. Lorca, Colleen G. Julian, Theresa L. Powell, Lorna G. Moore, and Thomas Jansson. "Effect of high altitude on human placental amino acid transport." Journal of Applied Physiology 128, no. 1 (January 1, 2020): 127–33. http://dx.doi.org/10.1152/japplphysiol.00691.2019.
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Women residing at high altitudes deliver infants of lower birth weight than at sea level. Birth weight correlates with placental system A-mediated amino acid transport capacity, and severe environmental hypoxia reduces system A activity in isolated trophoblast and the mouse placenta. However, the effect of high altitude on human placental amino acid transport remains unknown. We hypothesized that microvillous membrane (MVM) system A and system L amino acid transporter activity is lower in placentas of women living at high altitude compared with low-altitude controls. Placentas were collected at term from healthy pregnant women residing at high altitude (HA; >2,500 m; n = 14) or low altitude (LA; <1,700 m; n = 14) following planned, unlabored cesarean section. Birth weight, but not placenta weight, was 13% lower in HA pregnancies (2.88 ± 0.11 kg) compared with LA (3.30 ± 0.07 kg, P < 0.01). MVM erythropoietin receptor abundance, determined by immunoblot, was greater in HA than in LA placentas, consistent with lower placental oxygen levels at HA. However, there was no effect of altitude on MVM system A or L activity, determined by Na+-dependent [14C]methylaminoisobutyric acid uptake and [3H]leucine uptake, respectively. MVM abundance of glucose transporters (GLUTs) 1 and 4 and basal membrane GLUT4 were also similar in LA and HA placentas. Low birth weights in the neonates of women residing at high altitude are not a consequence of reduced placental amino acid transport capacity. These observations are in general agreement with studies of IUGR babies at low altitude, in which MVM system A activity is downregulated only in growth-restricted babies with significant compromise. NEW & NOTEWORTHY Babies born at high altitude are smaller than at sea level. Birth weight is dependent on growth in utero and, in turn, placental nutrient transport. We determined amino acid transport capacity in placentas collected from women resident at low and high altitude. Altitude did not affect system A amino acid transport across the syncytiotrophoblast microvillous membrane, suggesting that impaired placental amino acid transport does not contribute to reduced birth weight in this high-altitude population.
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Assad, R. S., F. Y. Lee, and F. L. Hanley. "Placental compliance during fetal extracorporeal circulation." Journal of Applied Physiology 90, no. 5 (May 1, 2001): 1882–86. http://dx.doi.org/10.1152/jappl.2001.90.5.1882.
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The fetus requires large amounts of volume when weaning from cardiac bypass. This suggests that placental vasculature can act as a large capacitor in the fetal circulation. To assess placental compliance of fetal lambs, seven isolated in situ lamb placentas were placed on extracorporeal circulation. Umbilical artery blood flow was varied from 0 to 350 ml · min−1· kg fetal wt−1. Because the extracorporeal circuit is a closed system, volume changes in the placenta induced by umbilical artery pressure changes were measured from reciprocal volume changes in the reservoir. There was a wide range of change in absolute volume of blood within the fetal placental compartment (216.4 ± 29.3 ml). Placental compliance was linear over the entire range of pressure changes exerted on the placental vasculature ( r2= 0.83, P = 0.0001). This indicates that the placenta is a unique and sensitive capacitor in the fetal circulation. This information is important clinically because it establishes that aggressive resuscitation of the fetus using volume may be necessary when weaning the fetus from cardiac bypass.
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Shanes, Elisheva D., Leena B. Mithal, Sebastian Otero, Hooman A. Azad, Emily S. Miller, and Jeffery A. Goldstein. "Placental Pathology in COVID-19." American Journal of Clinical Pathology 154, no. 1 (May 22, 2020): 23–32. http://dx.doi.org/10.1093/ajcp/aqaa089.
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Abstract Objectives To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. Results Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. Conclusions Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.
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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.
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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.
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Ordoñez, Maria Victoria, Giovanni Biglino, Massimo Caputo, Brenda Kelly, Aarthi Mohan, Johanna Trinder, and Stephanie L. Curtis. "Case of placental insufficiency and premature delivery in a Fontan pregnancy: physiological insights and considerations on risk stratification." Open Heart 8, no. 1 (February 2021): e001211. http://dx.doi.org/10.1136/openhrt-2019-001211.
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ObjectivesThe coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion.Methods and resultsWe analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings.ConclusionHistopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.
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Gardner, Sarah, Jennifer L. Grindstaff, and Polly Campbell. "Placental genotype affects early postpartum maternal behaviour." Royal Society Open Science 6, no. 9 (September 18, 2019): 190732. http://dx.doi.org/10.1098/rsos.190732.
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The mammalian placenta is a source of endocrine signals that prime the onset of maternal care at parturition. While consequences of placental dysfunction for offspring growth are well defined, how altered placental signalling might affect maternal behaviour is unstudied in a natural system. In the cross between sympatric mouse species, Mus musculus domesticus and Mus spretus , hybrid placentas are undersized and show misexpression of genes critical to placental endocrine function. Using this cross, we quantified the effects of placental dysregulation on maternal and anxiety-like behaviours in mice that differed only in pregnancy type. Relative to mothers of conspecific litters, females exposed to hybrid placentas did not differ in anxiety-like behaviours but were slower to retrieve 1-day-old pups and spent less time in the nest on the night following parturition. Early deficits in maternal responsiveness were not explained by reduced ultrasonic vocalization production in hybrid pups and there was no effect of pup genotype on measures of maternal behaviour and physiology collected after the first 24 h postpartum. These results suggest that placental dysregulation leads to poor maternal priming, the effect of which is alleviated by continued exposure to pups. This study provides new insight into the placental mediation of mother–offspring interactions.
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SIMCHENKO, A. V., O. A. ALEXEY, and A. A. KUPRASHVILI. "MITOCHONDRIAL DYSFUNCTION IN THE GENESIS OF PLACENTAL PATHOLOGY: PERINATAL OUTCOMES." MODERN PERINATAL MEDICAL TECHNOLOGIES IN SOLVING THE PROBLEM OF DEMOGRAPHIC SECURITY, no. 17 (December 2024): 357–61. https://doi.org/10.63030/2307-4795/2024.17.p.24.
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The human placenta is a unique organ with a temporary functioning period of about 280 days on average. All changes associated with the physiology of mitochondria, the aging process of the placenta, adaptation to changing conditions or dysfunction of the placenta directly affect the performance of the placenta's functions, as well as the development of the fetus. Modern studies studying the causes of intrauterine growth disorders of the fetus demonstrate the implementation of a chain of mechanisms of placental dysfunction, which leads to a slowdown in fetal growth with a subsequent slowdown in physical development at an early age. The literature review presents modern research in the field of studying the adaptive mechanisms of mitochondria during various periods of gestation and their relationship with neonatal pathology
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Levy, RA, E. Avvad, J. Oliveira, and LC Porto. "Placental pathology in antiphospholipid syndrome." Lupus 7, no. 2_suppl (February 1998): 81–85. http://dx.doi.org/10.1177/096120339800700218.
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One of the major targets of antiphospholipid antibodies (aPL) is the placenta, the evolution of which during pregnancy has been well documented. Histopathological findings are related to gestational age, and several physiologic and pathologic alterations that occur during its development. The major findings in placentae from aPL positive patients are thrombosis, acute atherosis, a decreased number of syncytio-vascular membranes, increased number of syncytial knots and obliterative arteriopathy. These findings are not specific to the antiphospholipid syndrome (APS) and sometimes do not correlate with the fetal outcome. Histopathological study of placentae may elucidate mechanisms of action of aPL in fetal loss and other obstetric complications. In addition, it may assist in the investigation of the differential diagnosis between APS and pregnancy-induced hypertension. Immunohistochemical studies of local placental proteins contribute to this differential diagnosis.
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Makaroun, Sami, and Katherine Himes. "Differential Methylation of Syncytin-1 and 2 Distinguishes Fetal Growth Restriction from Physiologic Small for Gestational Age." American Journal of Perinatology Reports 08, no. 01 (January 2018): e18-e24. http://dx.doi.org/10.1055/s-0038-1627473.
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Objective The retroviral genes encoding Syncytin-1 (SYN1) and Syncytin-2 (SYN2) are epigenetically regulated, uniquely expressed in the placenta and critical to placental function. We sought to determine if placental expression and methylation patterns of SYN1 and SYN2 from pregnancies complicated by fetal growth restriction (FGR) differed from physiologic small for gestational age (SGA) and appropriate for gestational age (AGA) controls. Study Design Placental biopsies were obtained from AGA, SGA and FGR neonates delivered at >36 weeks gestation. SGA and FGR were defined as birth weight <10% with FGR additionally requiring abnormal fetal testing. We quantified DNA methylation of SYN1 and SYN2 by EpiTyper and gene expression by RT-qPCR. Results We identified 10 AGA, 9 SGA and 7 FGR placentas. There was decreased methylation in SYN1 and SYN2 in FGR relative to AGA and SGA. When the sum of SYN1 and SYN2 methylation was used for prediction of FGR from SGA, the area under the receiver operator characteristic curve was 0.9048 (0.7602, 1). Conclusion SYN1 and SYN2 methylation marks differ in FGR and SGA. We plan future studies to examine these markers in cell free DNA to determine if these methylation changes could be used as a biomarker for FGR.
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Roberts, R. Michael, Jonathan A. Green, and Laura C. Schulz. "The evolution of the placenta." Reproduction 152, no. 5 (November 2016): R179—R189. http://dx.doi.org/10.1530/rep-16-0325.
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The very apt definition of a placenta is coined by Mossman, namely apposition or fusion of the fetal membranes to the uterine mucosa for physiological exchange. As such, it is a specialized organ whose purpose is to provide continuing support to the developing young. By this definition, placentas have evolved within every vertebrate class other than birds. They have evolved on multiple occasions, often within quite narrow taxonomic groups. As the placenta and the maternal system associate more intimately, such that the conceptus relies extensively on maternal support, the relationship leads to increased conflict that drives adaptive changes on both sides. The story of vertebrate placentation, therefore, is one of convergent evolution at both the macromolecular and molecular levels. In this short review, we first describe the emergence of placental-like structures in nonmammalian vertebrates and then transition to mammals themselves. We close the review by discussing the mechanisms that might have favored diversity and hence evolution of the morphology and physiology of the placentas of eutherian mammals.
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Gordon, Zoya, Osnat Eytan, Ariel J. Jaffa, and David Elad. "Hemodynamic analysis of Hyrtl anastomosis in human placenta." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 2 (February 2007): R977—R982. http://dx.doi.org/10.1152/ajpregu.00410.2006.
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The Hyrtl anastomosis is a common connection between the umbilical arteries near the cord insertion in most human placentas. It has been speculated that it equalizes the blood pressure between the territories supplied by the umbilical arteries. However, its functional role in the regulation and distribution of fetal blood flow to the placenta has not yet been explored. A computational model has been developed for quantitative analysis of hemodynamic characteristic of the Hyrtl anastomosis in cases of discordant blood flow in the umbilical arteries. Simulations were performed for cases of either increased placental resistance at the downstream end or reduced arterial blood flow due to some pathologies upstream of one of the arteries. The results indicate that when placental territories of one artery impose increased resistance to fetal blood flow, the Hyrtl anastomosis redistributes the blood flow into the second artery to reduce the large pressure gradients that are developed in the affected artery. When one of the arteries conducts a smaller blood flow into the placenta and a relatively smaller pressure gradient is developed, the Hyrtl anastomosis rebuilds the pressure gradients in the affected artery and redistributes blood flow from the unaffected artery to the affected one to improve placental perfusion. In conclusion, the Hyrtl anastomosis plays the role of either a safety valve or a pressure stabilizer between the umbilical arteries at the placental insertion.
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Willis, D. M., J. P. O'Grady, J. J. Faber, and K. L. Thornburg. "Diffusion permeability of cyanocobalamin in human placenta." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 250, no. 3 (March 1, 1986): R459—R464. http://dx.doi.org/10.1152/ajpregu.1986.250.3.r459.
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The molecular weight of cyanocobalamin is well suited to distinguish the two patterns of size discrimination found in the hemochorial and epitheliochorial placentas. The concentrations of cyanocobalamin that were used ensured that nondiffusional transport was negligible, and experiments on guinea pigs confirmed that the diffusion permeabilities measured with cyanocobalamin were the same as those expected for inert hydrophilic substances of similar molecular weight. All human studies were performed on volunteers who were scheduled for elective cesarean section under spinal or epidural anesthesia. Endogenous plasma concentrations of cobalamin were measured in 10 pregnant volunteers and their newborns. Ten additional volunteers were given 1 mg of cyanocobalamin by intramuscular injection 44 min before delivery. Placental permeability, calculated as the ratio of fetal uptake and the concentration-time integral between maternal and fetal plasmas, was 14.3 microliter X min-1 X g placental wt-1. The permeability of the human placenta parallels that of the histologically similar guinea pig placenta, at a slightly higher level, up to molecular weights of 1,355.
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Shearman, Lauren P., Alison M. McReynolds, Feng C. Zhou, and Jerrold S. Meyer. "Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta." American Journal of Physiology-Cell Physiology 275, no. 6 (December 1, 1998): C1621—C1629. http://dx.doi.org/10.1152/ajpcell.1998.275.6.c1621.
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We investigated the characteristics of cocainelike binding sites in rat placenta using [125I]RTI-55. [3H]paroxetine binding and immunocytochemical staining for serotonin [5-hydroxytryptamine (5-HT)] and for the 5-HT transporter were also used to obtain evidence for rat placental 5-HT uptake. [125I]RTI-55 saturation analyses with membranes from normal gestational day 20 placentas yielded curvilinear Scatchard plots that were resolved into high- and low-affinity components (mean dissociation constants of 0.29 and 7.9 nM, respectively). Drug competition studies with various monoamine uptake inhibitors gave rise to complex multiphasic displacement curves, although the results obtained with the selective 5-HT uptake inhibitor citalopram suggest that the 5-HT transporter is an important component of placental high-affinity [125I]RTI-55 binding. The presence of a rat placental 5-HT uptake system was additionally supported by the [3H]paroxetine binding experiments and by the presence throughout the placenta of immunoreactivity for 5-HT and the 5-HT transporter. Immunostaining with both antibodies was most intense in the junctional zone, whereas the density of [125I]RTI-55 binding sites was greater in the placental labyrinth. This discrepancy may be due to the fact that [125I]RTI-55 appears to be labeling additional cellular components besides the 5-HT transporter. The presence of cocaine- and antidepressant-sensitive 5-HT transporters in the placenta has important implications for the possible effects of these compounds on pregnancy and fetal development.
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Wilson, Rebecca L., Weston Troja, Emily K. Sumser, Alec Maupin, Kristin Lampe, and Helen N. Jones. "Insulin-like growth factor 1 signaling in the placenta requires endothelial nitric oxide synthase to support trophoblast function and normal fetal growth." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 320, no. 5 (May 1, 2021): R653—R662. http://dx.doi.org/10.1152/ajpregu.00250.2020.
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Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 growth factor ( hIGF1) gene delivery (NP-Plac1-hIGF1) increased hIGF1 expression and maintained fetal growth. However, whether it can restore fetal growth remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS−/−) mouse model, a genetic model of FGR, we found that despite inducing expression of hIGF1 in the placentas treated with NP-Plac1-hIGF1 ( P = 0.0425), FGR did not resolve. This was associated with no change to the number of fetal capillaries in the placental labyrinth; an outcome which was increased with NP-Plac1-hIGF1 treatment in the ligated mouse model, despite increased expression of angiopoietin 1 ( P = 0.05), and suggested IGF1 signaling in the placenta requires eNOS to modulate placenta angiogenesis. To further assess this hypothesis, BeWo choriocarcinoma cell line and human placental explant cultures were treated with NP-Plac1-hIGF1, oxidative stress was induced with hydrogen peroxide (H2O2), and NOS activity was inhibited using the inhibitor NG-monomethyl-l-arginine (l-NMMA). In both BeWo cells and explants, the protective effect of NP-Plac1-hIGF1 treatment against H2O2-induced cell death/lactate dehydrogenase release was prevented by eNOS inhibition ( P = 0.003 and P < 0.0001, respectively). This was associated with an increase in mRNA expression of oxidative stress markers hypoxia inducing factor 1α ( HIF1α; P < 0.0001) and ADAM10 ( P = 0.0002) in the NP-Plac1-hIGF1 + H2O2 + l-NMMA-treated BeWo cells. These findings show for the first time the requirement of eNOS/NOS in IGF1 signaling in placenta cells that may have implications for placental angiogenesis and fetal growth.
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Gibbens, Jacob, Shauna-Kay Spencer, Lucia Solis, Teylor Bowles, Patrick B. Kyle, Jamie L. Szczepanski, John Polk Dumas, Reanna Robinson, and Kedra Wallace. "Fas ligand neutralization attenuates hypertension, endothelin-1, and placental inflammation in an animal model of HELLP syndrome." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 319, no. 2 (August 1, 2020): R195—R202. http://dx.doi.org/10.1152/ajpregu.00272.2019.
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Neutralization of FasL is linked to suppression of hypertension, placental inflammation, and endothelin system activation in an animal model of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL), which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP syndrome decreases inflammation and placental apoptosis, improves endothelial damage, and improves hypertension. On gestational day (GD) 12, rats were chronically infused with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP rats on GD13 was used as a control for FasL antibody, and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis, and the degree of placental debris activation of endothelial cells. Administration of MFL4 to HELLP rats significantly decreased blood pressure compared with untreated HELLP rats and HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were significantly attenuated in response to MFL4 infusion, as were levels of placental and circulating TNFα when compared with untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed to placental debris and media from HP + MFL4 rats secreted significantly less endothelin-1 compared with stimulated endothelial cells from HELLP placentas. Neutralization of FasL is associated with decreased MAP and improvement in placental inflammation and endothelial damage in an animal model of HELLP syndrome.
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Zhao, Fusheng, Fang Lei, Xiang Yan, Senfeng Zhang, Wen Wang, and Yu Zheng. "Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats." Cellular Physiology and Biochemistry 48, no. 5 (2018): 1815–28. http://dx.doi.org/10.1159/000492504.
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Background/Aims: Cigarette smoke exposure (CSE) during pregnancy is a well-recognized health hazard that causes placental damage. Hydrogen sulfide (H2S) has been reported to protect multiple organs from injury. However, the protective effects of H2S have not been tested in the placenta. This study aimed to explore the potential of H2S in protecting placenta against oxidative injury induced by CSE during pregnancy and the possible underlying mechanisms. Methods: Pregnant SD rats were randomly divided into 4 groups: NaCl, NaHS (a donor of H2S), CSE and CSE+NaHS. Placental oxidative damage was detected by 8-hydroxy-2-deoxyguanosine (8-OHdG) stain and malondialdehyde (MDA) assay. Placental redox status was assessed by measuring reactive oxygen species (ROS), total antioxidant capacity (T-AOC) and glutathione (GSH) levels, as well as copper/zinc SOD (SOD1), manganese SOD (SOD2), catalase (CAT) and glutathione peroxidase (GPx) activities and expressions. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2) was analyzed by immunohistochemistry, real-time PCR and Western blot. Results: We found that NaHS markedly reduced the elevated levels of 8-OHdG and MDA induced by CSE. Further, NaHS treatment effectively mitigated CSE-induced placental redox imbalance by inhibiting ROS production, restoring T-AOC level, increasing GSH/GSSG ratio, and augmenting SOD1 SOD2, CAT and GPx activities and expressions. More notably, NaHS administration also reversed the aberrant decrease of Nrf2 due to CSE in rat placentas. Conclusion: Our data demonstrate that H2S can protect against CSE-induced placental oxidative damage probably by alleviating redox imbalance via Nrf2 pathway.
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Van Dyke, James U., Matthew C. Brandley, and Michael B. Thompson. "The evolution of viviparity: molecular and genomic data from squamate reptiles advance understanding of live birth in amniotes." REPRODUCTION 147, no. 1 (January 2014): R15—R26. http://dx.doi.org/10.1530/rep-13-0309.
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Squamate reptiles (lizards and snakes) are an ideal model system for testing hypotheses regarding the evolution of viviparity (live birth) in amniote vertebrates. Viviparity has evolved over 100 times in squamates, resulting in major changes in reproductive physiology. At a minimum, all viviparous squamates exhibit placentae formed by the appositions of maternal and embryonic tissues, which are homologous in origin with the tissues that form the placenta in therian mammals. These placentae facilitate adhesion of the conceptus to the uterus as well as exchange of oxygen, carbon dioxide, water, sodium, and calcium. However, most viviparous squamates continue to rely on yolk for nearly all of their organic nutrition. In contrast, some species, which rely on the placenta for at least a portion of organic nutrition, exhibit complex placental specializations associated with the transport of amino acids and fatty acids. Some viviparous squamates also exhibit reduced immunocompetence during pregnancy, which could be the result of immunosuppression to protect developing embryos. Recent molecular studies using both candidate-gene and next-generation sequencing approaches have suggested that at least some of the genes and gene families underlying these phenomena play similar roles in the uterus and placenta of viviparous mammals and squamates. Therefore, studies of the evolution of viviparity in squamates should inform hypotheses of the evolution of viviparity in all amniotes, including mammals.
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Shahnawaz, Saira, Usman Shah Nawaz, Jonas Zaugg, Ghulam Hussain, Nadia Malik, Muhammad Zahoor-ul-Hassan Dogar, Shoaib Ahmad Malik, and Christiane Albrecht. "Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage." Antioxidants 10, no. 11 (October 30, 2021): 1742. http://dx.doi.org/10.3390/antiox10111742.
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Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC transporters. We hypothesized that dysregulated autophagy and oxidative stress (OS) in the placenta leads to abnormal expression of membrane transporters contributing to poor pregnancy survival in EMC. We determined mRNA and protein expression of autophagy genes (Beclin-1/Bcl-2/LC3I/LC3II/p62) and ABC transporters (ABCA1/ABCG1/ABCG2) in placentae from EMC patients (n = 20), term controls (n = 19), first trimester (n = 6), and term controls (n = 5) controls. Oxidative/antioxidant status and biomarkers of oxidative damage were evaluated in maternal serum and placentae from EMC and healthy controls. In EMC, placental expression of LC3II/LC3I as well as of the key autophagy regulatory proteins Beclin-1 and Bcl-2 were reduced, whereas p62 was increased. Both in the serum and placentae of EMC patients, total OS was elevated reflected by increased oxidative damage markers (8-OHdG/malondialdehyde/carbonyl formation) accompanied by diminished levels of total antioxidant status, catalase, and total glutathione. Furthermore, we found reduced ABCG1 and increased ABCG2 expression. These findings suggest that a decreased autophagy status triggers Bcl-2-dependent OS leading to macromolecule damage in EMC placentae. The decreased expression of ABCG1 contributes to reduced cholesterol export to the growing fetus. Increasing ABCG2 expression could represent a protective feedback mechanism under inhibited autophagy conditions. In conclusion, dysregulated autophagy combined with increased oxidative toxicity and aberrant expression of placental ABC transporters affects materno-fetal health in EMC.
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Hata, Toshiyuki, and Sarah Cajusay-Velasco. "Three-dimensional Power Doppler Ultrasound Study of the Placenta." Donald School Journal of Ultrasound in Obstetrics and Gynecology 8, no. 4 (2014): 400–409. http://dx.doi.org/10.5005/jp-journals-10009-1380.
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ABSTRACT Advanced ultrasound technology has been a valuable tool in the assessment of placental anatomy and physiology. Conventional two-dimensional (2D) sonography reveals placental morphological characteristics, 2D color Doppler can assess blood flow in the placenta, 2D power Doppler can evaluate placental vascular trees, and three-dimensional (3D) ultrasound gives more detailed information on the surface anatomy. Recent advances, such as 3D power Doppler with virtual organ computer aided-analysis (VOCAL) and histogram analysis can measure the placental volume, and assess uteroplacental and fetoplacental perfusions. In particular, ‘placental vascular sonobiopsy’ can specifically evaluate the second- and thirdtrimester placental blood flow and vascularity by obtaining several spherical samples from the placenta that will represent the entire placenta. This article presents normal placental development and pathological findings of the placenta using 3D power Doppler ultrasound, and discusses 3D power Doppler assessments of placental perfusion in high-risk pregnancies, such as fetal growth restriction, pregnancy-induced hypertension and preeclampsia, and, from this basis, re-establishes the importance of 3D power Doppler ultrasound as a screening, diagnostic, and surveillance tool in normal and abnormal pregnancies. How to cite this article Tanaka H, Cajusay-Velasco S, Noguchi J, Hata T. Three-dimensional Power Doppler Ultrasound Study of the Placenta. Donald School J Ultrasound Obstet Gynecol 2014;8(4):400-409.
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Macias, Rocio I. R., Sonia Matilla, Elisa Lozano, Maria C. Estiú, Ronald P. Oude Elferink, and Jose J. G. Marin. "Role of the placenta in serum autotaxin elevation during maternal cholestasis." American Journal of Physiology-Gastrointestinal and Liver Physiology 315, no. 3 (September 1, 2018): G399—G407. http://dx.doi.org/10.1152/ajpgi.00112.2018.
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Intrahepatic cholestasis of pregnancy (ICP) is frequently accompanied by pruritus, whose etiology has been associated with an enhanced production of lysophosphatidic acid (LPA) by the combined action of phospholipase A1/A2 (PLA1/PLA2) and autotaxin (ATX). Here, we have investigated whether the placenta is involved in LPA release to maternal circulation during ICP. Serum levels of ATX and LPA (determined by ELISA) were elevated in women with ICP, and a correlation between both parameters was found. No relationship between serum levels of ATX or LPA and bile acids was found. Expression levels of ATX and PLA2 were determined by RT-qPCR and Western blot. Placenta ATX but not PLA2 was significantly upregulated in ICP, and a tendency to increase was found at the protein level. A correlation between serum ATX and placental ATX mRNA levels was found. In human placenta at term, ATX was clearly detected (by immunofluorescence) in Hofbauer cells, but only faintly in trophoblast cells. In pregnant rats, the expression of Atx and Pla2 in placenta was lower than in liver. When obstructive cholestasis was imposed by bile duct ligation from day 14 of gestation until term, placenta Atx and Pla2 expression was markedly enhanced, and overexpression was confirmed at the protein level for Pla2, whereas Atx protein was not detected. In conclusion, the placenta substantially participates in LPA production during gestation. This contribution is markedly higher during maternal cholestasis and hence, may be involved in ICP-associated pruritus. NEW & NOTEWORTHY Fetal placental macrophages and, to a lesser extent, trophoblast cells express high levels of autotaxin at term. An increased expression of mRNA and protein autotaxin, the key secretory enzyme responsible for the production of lysophosphatidic acid in serum, has been observed in placentas of women with cholestasis of pregnancy, which supports that the placenta can contribute to an increased production of this pruritogenic compound in women suffering from this liver disease.
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Soliman, Natasha. "HOW IT WORKS 5: PHYSIOLOGICAL BIRTH OF THE PLACENTA." Practising Midwife 27, no. 02 (March 1, 2024): 12–15. http://dx.doi.org/10.55975/nuap7898.
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In this article I talk about physiological birth of the placenta by exploring the anatomy and physiology of the placenta and its role in childbirth, pairing this with the skills required to facilitate a physiological placental birth. It is important for midwives to understand the anatomy and physiology behind the skill set required to provide care during physiological birth of the placenta and to understand how midwifery practice can influence achieving this for women and birthing people.
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Mark, P. J., J. L. Lewis, M. L. Jones, and B. J. Waddell. "158. THE UNFOLDED PROTEIN RESPONSE MAY CONTRIBUTE TO GLUCOCORTICOID-INDUCED PLACENTAL GROWTH RESTRICTION IN THE RAT VIA INCREASED PLACENTAL EXPRESSION OF HEAT SHOCK PROTEIN 70." Reproduction, Fertility and Development 22, no. 9 (2010): 76. http://dx.doi.org/10.1071/srb10abs158.
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Perturbations of normal endoplasmic reticulum (ER) physiology occur in a number of pathological conditions, including diabetes and preeclampsia. These pathologies are associated with elevated levels of inappropriately folded proteins and induction of ER stress. Accumulation of misfolded proteins induces the unfolded protein response which increases ER protein folding capacity and promotes ER-associated degradation of unfolded proteins. Glucocorticoids are essential for maturation of fetal organs, however excess exposure during pregnancy retards fetal and placental growth. Glucocorticoids also induce ER stress within macrophages, which reside within the placenta, and activate immune responses which can lead to oxidative stress and subsequent placental dysfunction. We hypothesised that excess glucocorticoid exposure would induce ER stress within the placenta and contribute to restriction of fetal and placental growth. This study compared placentas (n = 6/group) for control (Con) and dexamethasone-exposed pregnancies (Dex; 0.75 μg/mL drinking water from day 13 of gestation) at days 16 and 22 of gestation in the rat (term = 23 days). Placentas were dissected into junctional (JZ) and labyrinth (LZ) zones for separate analysis. Quantitative PCR was used to determine expression of mRNA for markers of ER stress, including heat shock factors (HSF-1 and HSF-2), heat shock proteins (HSP-70 and HSP-90) and C/EBP homologous protein (CHOP10). HSF-1 expression increased 2- to 4-fold from day 16 to 22 in both placental zones, but was not increased by glucocorticoids. Dex-exposure increased HSP-70 expression 2- to 3-fold in the LZ at both days of gestation, indicative of an ER stress response. Similar patterns for JZ expression of HSP-70 were observed. JZ expression of HSP-90 was also upregulated by Dex at day 22 but not day 16. CHOP10 was not induced by Dex-administration in either zone at either gestational time, which suggests that rather than activation of the ATF6/PERK pathway, the activation of ER stress is likely to be via XBP1 induction.
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Shaw, A. J., M. Z. Mughal, M. J. Maresh, and C. P. Sibley. "Sodium-dependent magnesium transport across in situ perfused rat placenta." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 2 (August 1, 1991): R369—R372. http://dx.doi.org/10.1152/ajpregu.1991.261.2.r369.
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Placentas of anesthetized rats were perfused in situ on the fetal side to study mechanisms of Mg2+ transport. The perfusate was a Mg(2+)-free Krebs-Ringer, and the unidirectional transfer of Mg2+ from maternal plasma to this Ringer was compared with that of 45Ca and 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with amiloride (0.5 mM) or ouabain (1 mM) both rapidly (4 min) reduced maternal-fetal clearance (Kmf) for Mg2+ but had no effect on Kmf for 45Ca. In contrast, perfusion of the carbonic anhydrase inhibitor acetazolamide (1 mM) did not affect Kmf for Mg2+ or 45Ca. Placental perfusion with a Na+-free Ringer reduced Kmf for both Mg2+ and 45Ca, although the latter response was delayed. Kmf for 51Cr-EDTA was increased by amiloride and was unaffected by perfusion of ouabain, acetazolamide, or Na+-free Ringer, indicating that the effects of these treatments on Kmf of Mg2+ do not reflect nonspecific effects on placental permeability. These data suggest that maternal-fetal transfer of Mg2+ across the perfused rat placenta is Na+ dependent.
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Yang, Xiaotao, Ping Xu, Fumei Zhang, Li Zhang, Yangxi Zheng, Mingyu Hu, Lulu Wang, et al. "AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia." Cellular Physiology and Biochemistry 49, no. 2 (2018): 578–94. http://dx.doi.org/10.1159/000492995.
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Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion.
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Mandò, Chiara, Valeria M. Savasi, Gaia M. Anelli, Silvia Corti, Anaïs Serati, Fabrizia Lisso, Chiara Tasca, Chiara Novielli, and Irene Cetin. "Mitochondrial and Oxidative Unbalance in Placentas from Mothers with SARS-CoV-2 Infection." Antioxidants 10, no. 10 (September 24, 2021): 1517. http://dx.doi.org/10.3390/antiox10101517.
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SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtDNA levels, DNA oxidative damage, expression levels of genes involved in antioxidant defenses, mitochondrial dynamics and respiratory chain subunits were investigated in placentas from singleton pregnancies of 30 women with SARS-CoV-2 infection during the third trimester (12 asymptomatic, 18 symptomatic) and 16 controls. mtDNA levels decreased in COVID-19 placentas vs. controls and inversely correlated with DNA oxidative damage, which increased in the symptomatic group. Antioxidant gene expressions decreased in SARS-CoV-2 mothers (CAT, GSS). Symptomatic cases also showed a lower expression of respiratory chain (NDUFA9, SDHA, COX4I1) and mt dynamics (DNM1L, FIS1) genes. Alterations in placental mitochondrial features and oxidative balance in COVID-19-affected mothers might be due to the impaired intrauterine environment, generated by systemic viral effects, leading to a negative vicious circle that worsens placental oxidative stress and mitochondrial efficiency. This likely causes cell homeostasis dysregulations, raising the potential of possible long-term effects.
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Barreto, Rodrigo da Silva Nunes, Ana Claudia Oliveira Carreira, Mônica Duarte da Silva, Leticia Alves Fernandes, Rafaela Rodrigues Ribeiro, Gustavo Henrique Doná Rodrigues Almeida, Bruna Tassia dos Santos Pantoja, Milton Yutaka Nishiyama Junior, and Maria Angelica Miglino. "Mice Placental ECM Components May Provide A Three-Dimensional Placental Microenvironment." Bioengineering 10, no. 1 (December 22, 2022): 16. http://dx.doi.org/10.3390/bioengineering10010016.
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Bioethical limitations impair deeper studies in human placental physiology, then most studies use human term placentas or murine models. To overcome these challenges, new models have been proposed to mimetize the placental three-dimensional microenvironment. The placental extracellular matrix plays an essential role in several processes, being a part of the establishment of materno-fetal interaction. Regarding these aspects, this study aimed to investigate term mice placental ECM components, highlighting its collagenous and non-collagenous content, and proposing a potential three-dimensional model to mimetize the placental microenvironment. For that, 18.5-day-old mice placenta, both control and decellularized (n = 3 per group) were analyzed on Orbitrap Fusion Lumos spectrometer (ThermoScientific) and LFQ intensity generated on MaxQuant software. Proteomic analysis identified 2317 proteins. Using ECM and cell junction-related ontologies, 118 (5.1%) proteins were filtered. Control and decellularized conditions had no significant differential expression on 76 (64.4%) ECM and cell junction-related proteins. Enriched ontologies in the cellular component domain were related to cell junction, collagen and lipoprotein particles, biological process domain, cell adhesion, vasculature, proteolysis, ECM organization, and molecular function. Enriched pathways were clustered in cell adhesion and invasion, and labyrinthine vasculature regulation. These preserved ECM proteins are responsible for tissue stiffness and could support cell anchoring, modeling a three-dimensional structure that may allow placental microenvironment reconstruction.
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Borke, James L., Ariel Caride, Anil K. Verma, Lucky K. Kelley, Carl H. Smith, John T. Penniston, and Rajiv Kumar. "Calcium pump epitopes in placental trophoblast basal plasma membranes." American Journal of Physiology-Cell Physiology 257, no. 2 (August 1, 1989): C341—C346. http://dx.doi.org/10.1152/ajpcell.1989.257.2.c341.
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The syncytiotrophoblast represents the primary cellular barrier between maternal and fetal circulations in the placenta. Large amounts of Ca2+ are transported across this barrier by mechanisms that are not clearly understood. To further understand this phenomenon, we examined rat and human placenta by immunohistochemical and protein blotting techniques with a monoclonal antibody raised against the human erythrocyte plasma membrane Ca2+ pump. Immunohistochemistry with this antibody showed specific staining in the human placenta of the basal (fetal facing) surface of the syncytiotrophoblast. In the rat placenta, immunohistochemistry also showed specific staining of the innermost (fetal facing) layer of the trophoblast and the basal surface of the endoderm of the intraplacental yolk sac. In Western blots of placental homogenates and membranes, the monoclonal antibody bound to a 140,000-mol wt band, characteristic of Ca2+ pumps in other tissues. Western blots of isolated basal membranes showed more intense staining than isolated microvillous membranes, confirming the results of the immunohistochemistry. In addition, Ca2+ transport in basal membrane vesicles from human placenta was inhibited by polyclonal antibodies prepared against the erythrocyte Ca2+ pump. We conclude that basal (fetal facing) layers of human and rat placentas contain a high-affinity Ca2+ pump situated to transport Ca2+ from the maternal to the fetal circulation. calcium-magnesium-adenosinetriphosphatase; calcium transport; immunohistochemistry; rat and human placenta Submitted on November 14, 1988 Accepted on March 27, 1989
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Bainbridge, Shannon A., and Graeme N. Smith. "The effect of nicotine on in vitro placental perfusion pressure." Canadian Journal of Physiology and Pharmacology 84, no. 8-9 (September 2006): 953–57. http://dx.doi.org/10.1139/y06-037.
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Cigarette smoking throughout pregnancy is associated with several negative outcomes, of which an increased incidence of intra-uterine growth restriction (IUGR) is most pronounced. Gestationally age-matched infants born to smoking mothers are, on average, 200 g lighter at birth, per pack smoked per day. The mechanisms and specific tobacco compounds responsible for the increased risk of IUGR among smokers have yet to be identified; however, it is widely accepted that smoking women have compromised placental perfusion throughout gestation due to the vasoconstricting effect of nicotine on uterine and placental blood vessels. Despite the universal acceptance of this theory, very little work has been completed to date examining the vasoactive properties of nicotine within the human placenta. The objective of this study was to determine the effect of nicotine on placental vascular function. Normal-term human placentae were obtained after elective cesarean sections. An in vitro placental perfusion system was used; increasing doses of nicotine (20–240 ng/mL) were added to either the maternal (n = 5) or fetal (n = 3) circulation. The basal feto-placental perfusion pressure was 39.87 ± 4.3 mmHg and was not affected by nicotine. This finding supports the hypotheses that nicotine does not directly affect placental microvascular function and that any contribution to fetal growth restriction is likely at the level of placental function (i.e., amino acid transport) and (or) uterine vascular function.
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Magnusson-Olsson, Anne Liese, Susanne Lager, Bo Jacobsson, Thomas Jansson, and Theresa L. Powell. "Effect of maternal triglycerides and free fatty acids on placental LPL in cultured primary trophoblast cells and in a case of maternal LPL deficiency." American Journal of Physiology-Endocrinology and Metabolism 293, no. 1 (July 2007): E24—E30. http://dx.doi.org/10.1152/ajpendo.00571.2006.
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Maternal hypertriglyceridemia is a normal condition in late gestation and is an adaptation to ensure an adequate nutrient supply to the fetus. Placental lipoprotein lipase (LPL) is involved in the initial step in transplacental fatty acid transport as it hydrolyzes maternal triglycerides (TG) to release free fatty acids (FFA). We investigated LPL activity and protein (Western blot) and mRNA expression (real-time RT-PCR) in the placenta of an LPL-deficient mother with marked hypertriglyceridemia. The LPL activity was fourfold lower, LPL protein expression 50% lower, and mRNA expression threefold higher than that of normal, healthy placentas at term ( n = 4–7). To further investigate the role of maternal lipids in placental LPL regulation, we isolated placental cytotrophoblasts from term placentas and studied LPL activity and protein and mRNA expression after incubation in Intralipid (as a source of TG) and oleic, linoleic, and a combination of oleic, linoleic, and arachidonic acids as well as insulin. Intralipid (40 and 400 mg/dl) decreased LPL activity by ≈30% ( n = 10–14, P < 0.05) and 400 μM linoleic and linoleic-oleic-arachidonic acid ( n = 10) decreased LPL activity by 37 and 34%, respectively. No major changes were observed in LPL protein or mRNA expression. We found no effect of insulin on LPL activity or protein expression in the cultured trophoblasts. To conclude, the activity of placental LPL is reduced by high levels of maternal TG and/or FFA. This regulatory mechanism may serve to counteract an excessive delivery of FFA to the fetus in conditions where maternal TG levels are markedly increased.
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Castillo-Castrejon, Marisol, Thomas Jansson, and Theresa L. Powell. "No evidence of attenuation of placental insulin-stimulated Akt phosphorylation and amino acid transport in maternal obesity and gestational diabetes mellitus." American Journal of Physiology-Endocrinology and Metabolism 317, no. 6 (December 1, 2019): E1037—E1049. http://dx.doi.org/10.1152/ajpendo.00196.2019.
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Pregnancies complicated by obesity and/or gestational diabetes (GDM) are associated with peripheral insulin resistance; however, the insulin responsiveness of the placenta in these pregnancy complications remains largely unknown. We tested the hypothesis that primary human trophoblast cells and placental villous explants will be insulin responsive, characterized by amino acid transport, Akt and Erk activity with maternal obesity, and/or GDM. We evaluated term placentas from women with normal body mass index (BMI) (normal; n = 15), obesity (OB; n = 11), normal BMI with GDM (N-GDM; n = 11), and obesity with GDM (OB-GDM; n = 11). In a subgroup, primary human trophoblast cells (PHT) were isolated, and in an independent subgroup placental villous explants were exposed to varying concentrations of insulin. Amino acid transport capacity and insulin signaling activity were determined. Insulin significantly increased amino acid transport activity to a similar degree in PHT cells isolated from normal (+21%), N-GDM (+38%), OB (+37%), and OB-GDM (+35%) pregnancies. Insulin increased Akt and Erk phosphorylation in PHT cells (3-fold) and in villous explants (2-fold) in all groups to a similar degree. In contrast to the peripheral maternal insulin resistance commonly associated with obesity and/or GDM, we found that the placenta is insulin sensitive in these pregnancy complications. We suggest that elevated maternal insulin levels in pregnancies complicated by obesity and/or GDM promote critical placental functions, including amino acid transport. Insulin-stimulated placental nutrient delivery may contribute to the increased risk of fetal overgrowth and adiposity in these pregnancies. Moreover, our findings may inform efforts to optimize insulin regimens for women with GDM.
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Kilpatrick, S. J., J. M. Roberts, D. L. Lykins, and R. N. Taylor. "Characterization and ontogeny of endothelin receptors in human placenta." American Journal of Physiology-Endocrinology and Metabolism 264, no. 3 (March 1, 1993): E367—E372. http://dx.doi.org/10.1152/ajpendo.1993.264.3.e367.
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Because of the potent mitogenic and vasoactive properties of endothelin-1 (ET-1) and the presence of its receptor in third trimester placenta, we postulated that ET-1 might be involved in human placental growth and vascularization during development. As an initial approach to test this hypothesis, placental ET receptors were characterized and quantified in each trimester of pregnancy. Membrane-rich particulates were prepared from first-, second-, and third-trimester villous human placenta obtained immediately after pregnancy termination or delivery. ET receptors were characterized by radioligand saturation analysis, ligand competition, and reverse transcription-polymerase chain reaction (RT-PCR) to determine the concentration, affinity, and specificity of ET binding sites, and to document the presence of specific ET-receptor subtype mRNA transcripts in placentas from each trimester. Kinetic determinations of 125I-labeled ET-1 binding yielded a Kd = 61 pM, consistent with the equilibrium determinations of 34 +/- 6 pM (n = 11). The concentration of ET receptors decreased significantly from 682 +/- 94 fmol/mg protein (n = 4) in the first trimester to 266 +/- 89 fmol/mg protein (n = 4) in the third trimester. Competition studies with unlabeled ET-1 indicated a single class of binding sites with a Ki = 49 +/- 5 pM (n = 9), whereas competition with ET-3 demonstrated binding sites with two affinities. The predominant sites had a Ki = 84 +/- 14 pM, similar to that for ET-1. The RT-PCR data confirmed that both ETA and ETB receptors mRNA transcripts are expressed in human placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
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Greupink, Rick. "1 Placental pharmacology studies to characterize the effects and disposition of pharmaceuticals: lessons from human tissues and cells for improving drug safety in pregnancy." Archives of Disease in Childhood 108, no. 6 (May 18, 2023): A1.1—A1. http://dx.doi.org/10.1136/archdischild-2023-esdppp.1.
Full textAbstract:
The placenta plays a key role in maintaining a healthy pregnancy. In order to improve drug safety during pregnancy, it is therefore relevant to understand to which extent and at which rate drugs are transferred across the placenta and how pharmaceuticals may affect placental function. Translational and predictive pharmacology studies based on human tissues and cells are becoming increasingly important in characterizing the effects and disposition of pharmaceuticals. With regard to the placenta, such approaches may for example be readily combined with physiology-based pharmacokinetic (PBPK) modeling to predict fetal exposure of drugs, as well as placental tissue exposure in the clinic. In addition, placental tissue and cells can be used to study potential effects of drugs, as well. The current presentation, will highlight several studies that investigated the placental disposition and effects of both small and large molecule pharmaceuticals, as well as how such data can help to better understand the clinical pharmacology of therapeutics.
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Elzinga, Femke A., Behrad Khalili, Daan J. Touw, Jelmer R. Prins, Peter Olinga, Henri G. D. Leuvenink, Harry van Goor, Sanne J. Gordijn, Anika Nagelkerke, and Paola Mian. "Placenta-on-a-Chip as an In Vitro Approach to Evaluate the Physiological and Structural Characteristics of the Human Placental Barrier upon Drug Exposure: A Systematic Review." Journal of Clinical Medicine 12, no. 13 (June 27, 2023): 4315. http://dx.doi.org/10.3390/jcm12134315.
Full textAbstract:
Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g., cord blood sampling) and ex vivo (e.g., placenta perfusion) models have inherent limitations. A placenta-on-a-chip model is a promising alternative. A systematic search was performed in PubMed on 2 February 2023, and Embase on 14 March 2023. Studies were included where placenta-on-a-chip was used to investigate placental physiology, placenta in different obstetric conditions, and/or fetal exposure to maternally administered drugs. Seventeen articles were included that used comparable approaches but different microfluidic devices and/or different cultured maternal and fetal cell lines. Of these studies, four quantified glucose transfer, four studies evaluated drug transport, three studies investigated nanoparticles, one study analyzed bacterial infection and five studies investigated preeclampsia. It was demonstrated that placenta-on-a-chip has the capacity to recapitulate the key characteristics of the human placental barrier. We aimed to identify knowledge gaps and provide the first steps towards an overview of current protocols for developing a placenta-on-a-chip, that facilitates comparison of results from different studies. Although models differ, they offer a promising approach for in vitro human placental and fetal drug studies under healthy and pathological conditions.
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John, Rosalind M. "Epigenetic regulation of placental endocrine lineages and complications of pregnancy." Biochemical Society Transactions 41, no. 3 (May 23, 2013): 701–9. http://dx.doi.org/10.1042/bst20130002.
Full textAbstract:
A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495–532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.
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Lazo-de-la-Vega-Monroy, Maria-Luisa, Karen-Alejandra Mata-Tapia, Juan-Antonio Garcia-Santillan, Maria-Angelica Corona-Figueroa, Martha-Isabel Gonzalez-Dominguez, Hector-Manuel Gomez-Zapata, Juan-Manuel Malacara, Leonel Daza-Benitez, and Gloria Barbosa-Sabanero. "Association of placental nutrient sensing pathways with birth weight." Reproduction 160, no. 3 (September 2020): 455–68. http://dx.doi.org/10.1530/rep-20-0186.
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Birth weight (BW) is an important indicator for newborn health. Both high and low BW is associated with increased risks for adult metabolic diseases. AMPK (AMP-activated protein kinase), mTOR (mechanistic target of rapamycin), and insulin/IGF1 (insulin-like growth factor 1) pathways may function as placental sensors of maternal hormonal and nutritional status. However, the physiological role of these pathways in placenta has not been completely elucidated. To evaluate expression and activation of AMPK, mTOR, and insulin/IGF1 pathways and its association with placental weight (PW), BW, and maternal hormonal and metabolic status, we performed a cross-sectional study in placentas from non-obese mothers with SGA (n = 17), AGA (n = 19) and LGA (n = 10) newborns. We analyzed placental expression of total and phosphorylated key proteins from the AMPK, mTOR and insulin/IGF1 pathways. Maternal and cord blood hormones were determined by ELISA. AMPK and LKB1 activation correlated negatively with PW and BW, cord leptin, and pregestational BMI. Placental SIRT1 inversely correlated with BW, cord leptin, neonatal HOMA-IR, and maternal IGF1. PGC1α correlated negatively with PW and BW. Phosphorylated mTOR positively correlated with maternal glucose, PW and BW. IGF1R was lower in SGA. No changes in p-IGF1R, INSRb, total AKT or p-AKT were found, and pPDK1 was lower in SGA and LGA. These results suggest that placental AMPK, insulin/IGF1, and mTOR pathways may influence fetal growth, perhaps regulating placental physiology, even in metabolically healthy pregnancies. Our study highlights these nutrient sensing pathways as potential molecular mechanisms modulating placental adaptations and, thus, long-term metabolic health.
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Watson, Erica D., and James C. Cross. "Development of Structures and Transport Functions in the Mouse Placenta." Physiology 20, no. 3 (June 2005): 180–93. http://dx.doi.org/10.1152/physiol.00001.2005.
Full textAbstract:
The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.
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Zhang, Xue Mei, Xi Xiong, Chao Tong, Qin Li, Shuai Huang, Qing Shu Li, Ya Ming Liu, et al. "Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway." Cellular Physiology and Biochemistry 51, no. 5 (2018): 2030–40. http://dx.doi.org/10.1159/000495822.
Full textAbstract:
Background/Aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. Methods: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). Results: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn’t show significant difference between PE and normal placentas. Conclusion: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.
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Paterson, P. G., B. Sarkar, and S. H. Zlotkin. "The effect of zinc levels in fetal circulation on zinc clearance across the in situ perfused guinea pig placenta." Canadian Journal of Physiology and Pharmacology 68, no. 11 (November 1, 1990): 1401–6. http://dx.doi.org/10.1139/y90-213.
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Although zinc is essential for normal fetal growth and development, little is known about factors that influence its transfer across the placenta. The in situ perfused guinea pig placenta model was used to study the influence of the zinc concentration of fetal circulation on maternofetal placental zinc transfer. A placenta of the anaesthetized sow was perfused (on the fetal side) with a physiological perfusate via the umbilical vessels, with the fetus excluded. The sow was infused intravenously with 65zinc as a tracer of placental Zn clearance, and with antipyrine as an indirect indicator of maternal placental blood flow. Maternal plasma and placental effluent samples collected at intervals were counted for 65zinc by gamma counter, and the absorbance of nitrosated antipyrine was measured at 350 nm. Varying the mean zinc concentration in the perfusate from 0.176 to 1.87 mg/L had no effect on relative zinc clearance calculated as zinc clearance/antipyrine clearance (mean ± SEM; 0.085 ± 0.010 vs. 0.114 ± 0.018; n = 6; p > 0.05). The results suggest that short-term changes in fetal zinc status do not influence placental zinc transfer.Key words: placenta, zinc, transport, trophoblast.
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Visiedo, Francisco, Fernando Bugatto, Viviana Sánchez, Irene Cózar-Castellano, Jose L. Bartha, and Germán Perdomo. "High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta." American Journal of Physiology-Endocrinology and Metabolism 305, no. 2 (July 15, 2013): E205—E212. http://dx.doi.org/10.1152/ajpendo.00032.2013.
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Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ∼30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ∼20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ∼40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ∼70% and phosphorylation levels of acetyl-CoA carboxylase by ∼25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides.
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Ali, Asghar, Frieder Hadlich, Muhammad W. Abbas, Muhammad A. Iqbal, Dawit Tesfaye, Gerrit J. Bouma, Quinton A. Winger, and Siriluck Ponsuksili. "MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers." International Journal of Molecular Sciences 22, no. 5 (February 25, 2021): 2313. http://dx.doi.org/10.3390/ijms22052313.
Full textAbstract:
Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes.
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Jin, Yan, Hana Vakili, Song Yan Liu, Savas Menticoglou, Margaret E. Bock, and Peter A. Cattini. "Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity." American Journal of Physiology-Endocrinology and Metabolism 315, no. 4 (October 1, 2018): E435—E445. http://dx.doi.org/10.1152/ajpendo.00042.2018.
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The human (h) placental lactogenic hormone chorionic somatomammotropin (CS) is highly produced during pregnancy and acts as a metabolic adaptor in response to maternal insulin resistance. Maternal obesity can exacerbate this “resistance”, and a >75% decrease in CS RNA levels was observed in term placentas from obese vs. lean women. The genes coding for hCS ( hCS-A and hCS-B) and placental growth hormone ( hGH-V) as well as the hCS-L pseudogene and pituitary growth hormone (GH) gene ( hGH-N) are located at a single locus on chromosome 17. Three remote hypersensitive sites (HS III–V) located >28 kb upstream of hGH-N as well as local hCS gene promoter and enhancer regions are implicated in hCS gene expression. A placenta-specific chromosomal architecture, including interaction between HS III–V and hCS but not hGH gene promoters, was detected in placentas from lean women (BMI <25 kg/m2) by using the chromosome conformation capture assay. This architecture was disrupted by pre-pregnancy maternal obesity (BMI >35 kg/m2), resulting in a predominant interaction between HS III and the hGH-N promoter, which was also observed in nonplacental tissues. This was accompanied by a decrease in hCS levels, which was consistent with reduced RNA polymerase II and CCAAT/enhancer-binding protein-β association with individual hCS promoter and enhancer sequences, respectively. Thus, pre-pregnancy maternal obesity disrupts the placental hGH/CS gene locus chromosomal architecture. However, based on data from obese women who develop GDM, insulin treatment partially recapitulates the chromosomal architecture seen in lean women and positively affects hCS production, presumably facilitating prolactin receptor-related signaling by hCS.
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Wieser, Fritz, Leslie Waite, Christophe Depoix, and Robert N. Taylor. "PPAR Action in Human Placental Development and Pregnancy and Its Complications." PPAR Research 2008 (2008): 1–14. http://dx.doi.org/10.1155/2008/527048.
Full textAbstract:
During pregnancy crucial anatomic, physiologic, and metabolic changes challenge the mother and the fetus. The placenta is a remarkable organ that allows the mother and the fetus to adapt to the new metabolic, immunologic, and angiogenic environment imposed by gestation. One of the physiologic systems that appears to have evolved to sustain this metabolic regulation is mediated by peroxisome proliferator-activated receptors (PPARs). In clinical pregnancy-specific disorders, including preeclampsia, gestational diabetes, and intrauterine growth restriction, aberrant regulation of components of the PPAR system parallels dysregulation of metabolism, inflammation and angiogenesis. This review summarizes current knowledge on the role of PPARs in regulating human trophoblast invasion, early placental development, and also in the physiology of clinical pregnancy and its complications. As increasingly indicated in the literature, pregnancy disorders, such as preeclampsia and gestational diabetes, represent potential targets for treatment with PPAR ligands. With the advent of more specific PPAR agonists that exhibit efficacy in ameliorating metabolic, inflammatory, and angiogenic disturbances, further studies of their application in pregnancy-related diseases are warranted.
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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.
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Waddell, B. J. "056. EUTHERIAN MAMMALS DO IT DIFFERENTLY: PLACENTAL ENDOCRINE STRATEGIES FOR THE MAINTENANCE OF PREGNANCY IN RODENTS AND PRIMATES." Reproduction, Fertility and Development 22, no. 9 (2010): 17. http://dx.doi.org/10.1071/srb10abs056.
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The placenta of rats and humans share important anatomical similarities, each with a chorio-allantoic, single discoid, haemochorial structure that facilitates highly efficient nutrient transport. Importantly, however, these similarities reflect convergent evolution and conceal markedly different developmental trajectories and endocrine functions. Placental endocrine signals are essential to drive maternal adaptations that facilitate fetal development and ultimately successful birth. Central to these adaptations is a sustained increase in production of the sex steroids progesterone and oestrogen, each driven by very different placental signalling in rodents and primates. Specifically, while the rat placenta supplies androgen precursors for ovarian (luteal) oestrogen synthesis, in humans and closely-related primates the fetal adrenal cortex supplies androgen precursors for placental oestrogen synthesis. In both cases the resultant increase in oestrogen provides a local stimulus to ovarian (rat) and placental (primate) progesterone synthesis. This shift from a placental-ovarian to a feto-placental unit for oestrogen synthesis in primates may have evolved to ensure greater fetal influence over maternal adaptations. Placental regulation of maternal physiology is also mediated via a third steroid group, the glucocorticoids, which promote a successful pregnancy outcome via effects on maternal metabolism and fetal organ maturation. Glucocorticoids are produced within the HPA axis, activity of which is enhanced by the placenta (eg, via oestrogen in rodents and CRH in primates). Moreover, the placenta regulates access of maternal glucocorticoids to the fetus via expression of the 11 b -HSD enzymes which constitute the placental glucocorticoid barrier. Intriguingly, this barrier effectively disappears during late fetal life in rodents but increases markedly in primates (notably baboons and humans). We hypothesise that this opposite developmental change is due in part to the evolution of the feto-placental unit for oestrogen synthesis in these primate species, and the associated need to prevent suppression of the fetal HPA axis by maternal glucocorticoids in late gestation.