Conservation at the uterine-placental interface
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ABSTRACT:
PROVIDER: PRJNA849158 | ENA |
REPOSITORIES: ENA
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Project description:The hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus. This is not a consistent feature of hemochorial placentation and has hindered the establishment of suitable animal models. The rat represents an intriguing model for investigating hemochorial placentation with deep trophoblast cell invasion. In this study, we used single cell RNA sequencing to characterize the transcriptome of the invasive trophoblast cell lineage, as well as other cell populations within the rat uterine-placental interface during early (gestation day, gd, 15.5) and late (gd 19.5) stages of intrauterine trophoblast cell invasion. We identified a robust set of transcripts that define invasive trophoblast cells, as well as transcripts that distinguished endothelial, smooth muscle, natural killer, and macrophage cells. Invasive trophoblast, immune, and endothelial cell populations exhibited distinct spatial relationships within the uterine-placental interface. Furthermore, the maturation stage of invasive trophoblast cell development could be determined by assessing gestation-stage dependent changes in transcript expression. Finally, and most importantly, expression of a prominent subset of rat invasive trophoblast cell transcripts is conserved in the invasive extravillous trophoblast cell lineage of the human placenta. These findings provide foundational data to identify and interrogate key conserved regulatory mechanisms essential for development and function of an important compartment within the hemochorial placentation site that is essential for a healthy pregnancy.
2022-09-20 | GSE206086 | GEO
Project description:After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or pre-eclampsia (PE). Placental growth factor (PlGF) can increase cell stiffness contributing to pathological angiogenesis but the biomechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine vasculature by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signalling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signalling. Taken together, perturbed PlGF-NFAT5-SGK1 mechano-signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs -endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.
2024-10-17 | PXD051697 | Pride
Project description:Microarray analysis of differentially expressed genes from rats undergoing placental ischemia versus health controls Placental ischemia is believed to be an important contributor to human preeclampsia, though the targets induced by the ischemia remain unclear. Chorionic placental tissues from 6 control and 6 placental ischemic reduced uterine perfusion pressure (RUPP) rats were analyzed for gene expression by microarray.
2013-09-05 | E-GEOD-50596 | biostudies-arrayexpress
Project description:Maternal and fetal monocytes and tissue macrophages (decidual macrophages, Hofbauer cells) at the feto-maternal interface have different methylome. Paired and balanced design. We compared maternal blood monocytes (MB) vs. cord blood monocytes (CB), maternal blood monocytes (MB) vs. decidual macrophages (Deci), cord blood monocytes (CB) vs placental macrophages (villi) and decidual macrophages (Deci) vs. placental macrophages (villi).
2011-11-15 | E-GEOD-31680 | biostudies-arrayexpress
Project description:The hemochorial placenta provides a critical barrier at the maternal-fetal interface to modulate maternal immune tolerance and enable gas and nutrient exchange between mother and conceptus. Pregnancy outcomes are adversely affected by gestational diabetes mellitus (GDM); however, the effects of GDM on placental formation, and subsequently fetal development, are not fully understood. In this report, streptozotocin was used to induce hyperglycemia in pregnant rats for the purpose of investigating the impact of GDM on placental formation and fetal development. GDM caused placentomegaly and placenta malformation, decreasing placental efficiency and fetal size. Elevated glucose disrupted rat trophoblast stem (TS) cell differentiation in vitro. Evidence of altered trophoblast differentiation was also observed in vivo, as hyperglycemia affected the junctional zone transcriptome and interfered with intrauterine trophoblast invasion and uterine spiral artery remodeling. When exposed to hypoxia, rats with GDM showed decreased proliferation and ectoplacental cone development on gestation day (gd) 9.5 and complete pregnancy loss by gd 13.5. Furthermore, elevated glucose concentrations inhibited TS cell responses to hypoxia in vitro. Overall, these results indicate that alterations in placental development, efficiency, and plasticity could contribute to the suboptimal fetal outcomes in offspring from pregnancies complicated by GDM.
2020-07-07 | GSE144276 | GEO
Project description:High uterine artery Doppler (UtAD) resistance indices (RI), indicative of poor uterine blood flow, have been shown to be predictive of placental complications of pregnancy such as pre-eclampsia (PE), fetal growth restriction (FGR) and stillbirth. A comparative analysis of gene expression in High vs normal risk pregnancies in placental tissue from first trimester was undertaken. Patients were stratified by their risk of developing placental complications as determined by Doppler resistance indices. High-resistance cases were defined as those with bilateral uterine diastolic notches and a mean RI >95th percentile whilst Normal-resistance cases had a mean RI of <95th percentile. A direct comparison of gene expression in Placental villous tissue obtained folowing terminations at of 9 to 14 weeks gestation.
2015-07-22 | E-MTAB-3265 | biostudies-arrayexpress
Project description:The placenta acts as an interface between the mother and fetus, regulating nutrient transport and secreting hormones which impact maternal metabolism. Complications during pregnancy, such as placental endocrine malfunction, programme offspring to develop metabolic disease during adulthood, in part via changes in gene expression in critical metabolic organs, such as the liver, during fetal development. Placental endocrine malfunction was induced via the misexpression of two imprinted genes (Igf2 and H19) exclusively in the endocrine zone of the mouse placenta, to study the consequences this has on fetal hepatic gene expression.
2023-11-30 | E-MTAB-11457 | biostudies-arrayexpress
Project description:Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. An unbiased transcriptomic analysis of healthy mouse placenta revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysfunction and cellular senescence. We validated these gestational age-associated changes through similar findings in human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma JAR cells, we modeled HIF-1 induction using prolyl hydroxylase inhibitors cobalt chloride (CoCl2) and dimethyloxalylglycine (DMOG), and demonstrated that mitochondrial dysfunction and cellular senescence occur secondary to HIF-1 stabilization. Whole transcriptome analysis revealed that HIF-1 stabilization in JAR cells recapitulated the dysregulation of several pathways observed in aged placenta. Further, conditioned media from cultured trophoblasts following HIF-1 induction is sufficient to induce a contractile phenotype in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may help drive the transition from uterine quiescence to contractility at the onset of labor.
2022-03-29 | GSE199278 | GEO
Project description:Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of 3rd trimester pregnant pigs can result in transmission of the virus to the fetus and ultimately death in utero or postnatally. Little is known about the immune response to infection at the maternal-fetal interface and in the fetus itself, or the molecular events behind virus transmission and disease progression in the fetus. To investigate these processes, RNA-sequencing of two tissues, uterine endothelium adjacent to the umbilical attachment site and fetal thymus, was performed 21 days post challenge on four groups of fetuses selected from a large PRRSV challenge experiment of pregnant gilts. RNA-seq experiment compared gene expression between four different groups of fetuses (n=12 per group): control (CON-uninfected fetuses from mock inoculated gilts), UNINF (uninfected fetuses from PRRSV-inoculated gilts), INF (infected fetuses from PRRSV-inoculated gilts), and meconium-stained fetuses (MEC-meconium-stained fetuses from PRRSV-inoculated gilts) and investigated two tissues: uterine endometrium (with adherent placental tissue) at the site of umbilical attachment and fetal thymus (96 samples in total). Three contrasts were performed for the differential expression (edgeR) and network (WGCNA) analyses: UNINF v CON, INF v UNINF, and MEC v INF.
2016-05-17 | E-GEOD-71205 | biostudies-arrayexpress
Project description:Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In?this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome? by assessing the gene expression of receptor-ligand pairs across cell types. Moreover, we find that the expression of G-protein coupled receptors is highly cell-type?specific, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a relatively large?number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability ?to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, suggesting a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene ?expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast.
2017-01-25 | GSE87692 | GEO