G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE183879 | GEO | 2021/09/12
REPOSITORIES: GEO
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Project description:Insufficient invasion of trophoblast cells into the uterine decidua is associated with preeclampsia (PE). G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. GPER is expressed in human trophoblast cells and downregulated GPER levels are noted in PE. However, to date, the role of GPER in trophoblast cells remains largely unknown. Here, we applied RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to G1, an agonist of GPER, and identified angiopoietin-like 4 (ANGPTL4) as a target gene of GPER. Treatment of trophoblast cells with G1 or 17β-estradiol (E2) activated Yes-associated protein (YAP), the major downstream effector of the Hippo pathway, via GPER but in a mammalian STE20-like protein kinase 1 (MST1)-independent manner. Using pharmacological inhibitors as well as loss- and gain-of-function approaches, our results revealed that YAP activation was required for GPER-stimulated ANGPTL4 expression. Transwell invasion assays demonstrated that activation of GPER-induced ANGPTL4 promoted cell invasion. In addition, the expression levels of GPER, YAP, and ANGPTL4 were downregulated in the placenta of patients with PE. Our findings reveal a mechanism by which GPER exerts its stimulatory effect on human trophoblast cell invasion by upregulating YAP-mediated ANGPTL4 expression.
| S-EPMC8589964 | biostudies-literature
Project description:Placentation requires the proper regulation of extravillous trophoblast (EVT) migration and invasion into the decidua and maternal vasculature, processes which are initiated in physiologic hypoxic conditions. Abnormal EVT migration and/or invasion have been suggested to lead to pregnancy complications, such as preeclampsia. The objectives of this study are to determine how exposure to hypoxia impacts gene expression and cellular motility of first trimester trophoblasts, and to assess if expression of migration-associated genes is dysregulated in 2nd trimester chorionic villous samples (CVS) from preeclampsia pregnancies relative to CVS from healthy pregnancies. The 1st trimester trophoblast cell line, HTR8/SVneo, was used to investigate the relationship between hypoxia and Notch signaling in trophoblast migration and invasion. RNA sequencing and quantitative RT-PCR analyses show that exposure to hypoxia (2.5% O2) activates Notch signaling in HTR-8/SVneo. We demonstrate that exposure of HTR-8/SVneo to hypoxia induces expression of genes associated with cellular migration and invasion and increases HTR-8/SVneo cellular migration and invasion, whereas inhibition of gamma-secretase decreases Notch signaling and decreases HTR-8/SVneo migration and invasion. Analysis of RNA sequencing data from CVS of preeclampsia and uncomplicated pregnancies identified significant differentially expressed genes that are involved in cellular migration and invasion. Decreased expression of migration and invasion genes in CVS from preeclampsia pregnancies, may impair trophoblast migration and invasion in the 2nd trimester of pregnancy, resulting in the development of preeclampsia.
2021-08-05 | GSE155750 | GEO
Project description:Invasive extravillous trophoblasts (EVTs) of the human placenta are critically involved in successful pregnancy outcome since they remodel the uterine spiral arteries to increase blood flow and oxygen delivery to the placenta and the developing fetus. To gain more insights into their biological role different primary cell culture models are commonly utilised. However, access to early placental tissue may be limited and primary trophoblasts rapidly cease proliferation in vitro impairing genetic manipulation. Hence, trophoblastic cell lines have been widely used as surrogates to study EVT function. Although the cell lines share some molecular marker expression with their primary counterpart, it is unknown to what extent they recapture the invasive phenotype of EVT. Therefore, we here report the first thorough GeneChip analyses of SGHPL-5, HTR-8/SVneo, BeWo, JEG-3 and the novel ACH-3P trophoblast cells in comparison to previously analysed primary villous cytrophoblasts and extravillous trophoblasts. To identify EVT-specific gene expression signatures in trophoblast cell lines, we calcuted differentially expressed genes between pre-defined groups based on the distinct origins of the five trophoblast cell lines under investigation. Comparison 1 comprised EVT, HTR-8/Svneo and SGHPL-5 vs choriocarcinoma cells (ACH-3P, BeWo, JEG-3). Comparison 2 comprised EVT, ACH-3P, BeWo, JEG-3 vs extravillous trophoblast cell lines (HTR-8/SVneo, SGHPL-5).
2010-09-23 | E-GEOD-20510 | biostudies-arrayexpress
Project description:KDM5C is a H3K4- specific demethylase, which has multiple biological roles in development and disease. However, the role of KDM5C in trophoblasts at the maternal-fetal interface remains unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from patient with recurrent miscarriage (RM). Trophoblasts proliferation and invasion was inhibited by KDM5C overexpression and was enhanced by KDM5C knockdown. Interestingly, KDM5C knockdown promoted trophoblast invasion in villous explant culture system. RNA-seq and ChIP-seq analyses revealed that KDM5C exerts anti-proliferation and anti-invasion effect by directly modulating H3K4 methylation level to repress the expression of a number of key regulatory genes. We show that two of these genes, TGFβ2, RAGE, are essential for the proliferation and invasion of trophoblasts. Taken together, our results show that the KDM5C is regulator of trophoblast function during early pregnancy and indicated that KDM5C may be involved in the pathogenesis of RM. Next Generation Sequencing Facilitates Quantitative Analysis of HTR-8/SVneo cells transduced with control or KDM5C-expression vector, and HTR-8/SVneo cells transduced with NC or KDM5C shRNA-expression vector,
2022-12-16 | GSE141716 | GEO
Project description:To characterize genome-wide KDM5C traget genes in HTR-8/SVneo cells transduced with KDM5C-expression vector by CUT&Tag.
2022-12-16 | GSE200540 | GEO
Project description:G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression
| PRJNA762271 | ENA
Project description:Aberrantexpression of long non-coding RNAs (lncRNAs) has been reported to play a crucial role in the biological function of trophoblasts and contribute to preeclampsia (PE). Our previous study demonstrated that MIR193BHG is increased in preeclamptic placental tissues. In this study, we further explored the effects of MIR193BHG on the function of trophoblast cells and attempted to elucidate its underlying molecular mechanisms. Results showed that MIR193BHG was predominantly localized in the nucleus of HTR-8/SVneo cells. Overexpression of MIR193BHG significantly inhibited proliferation, migration and invasion of HTR-8/SVneo cells, while increasing apoptosis. Knockdown of MIR193BHG produced opposite effects.Furthermore, overexpression of MIR193BHG led to significant increases in both mRNA and protein levels of p53 compared with the control group. More importantly, knockdown of p53 rescued the negative effects induced by overexpressed MIR193BHG on cell proliferation, migration, and invasion while partially counteracting its apoptotic effects on HTR-8/SVneo cells. In conclusion, our findings suggest that MIR193BHG played a critical role in the progression of PE by regulating the expression of p53 and may serve as a novel therapeutic target for PE.
2023-10-16 | GSE245279 | GEO
Project description:Chronical hypoxia is a common occurrence following reduced uteroplacental blood flow resulting from incomplete trophoblast invasion and abnormal vascular remodeling of the spiral arteries in PE. Hypoxia can lead to active glycolysis, which increases the production of lactate, a substrate for histone lactylation. To screen for genes that may be regulated by histone lactylation in PE placentas, we performed RNA-seq in HTR-8/SVneo cells under hypoxia or treated with sodium L-lactate. The results showed that 3578 genes were upregulated in the HTR-8/SVneo cells under hypoxia compared to those under normoxia, and 355 genes were upregulated in HTR-8/SVneo cells treated with sodium L-lactate compared to the control cells. 152 upregulated genes in the HTR-8/SVneo cells under hypoxia and those treated with sodium L-lactate overlapping.
2021-12-13 | GSE190694 | GEO
Project description:KDM5C is a H3K4- specific demethylase, which has multiple biological roles in development and disease. However, the role of KDM5C in trophoblasts at the maternal-fetal interface remains unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from patient with recurrent miscarriage (RM). Trophoblasts proliferation and invasion was inhibited by KDM5C overexpression and was enhanced by KDM5C knockdown. Interestingly, KDM5C knockdown promoted trophoblast invasion in villous explant culture system. RNA-seq and ChIP-seq analyses revealed that KDM5C exerts anti-proliferation and anti-invasion effect by directly modulating H3K4 methylation level to repress the expression of a number of key regulatory genes. We show that two of these genes, TGFβ2, RAGE, are essential for the proliferation and invasion of trophoblasts. Taken together, our results show that the KDM5C is regulator of trophoblast function during early pregnancy and indicated that KDM5C may be involved in the pathogenesis of RM. To characterize genome-wide H3K4me3 chromatin-state of HTR-8/SVneo cells.
2022-12-16 | GSE141717 | GEO
Project description:The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which are required for embryo implantation) and evaluate the potential involvement of endometrial extracellular vesicles (EVs) in the regulation of these physiological processes. Using primary human cell cultures, we first demonstrated that obesity is associated with significantly lower in vitro decidualization of endometrial stromal cells (ESCs). We then showed that the trophoblastic cell line’s invasive ability was greater in the presence of conditioned media from cultures of ESCs from obese women. Using mass-spectrometry-based quantitative proteomics, we found that EVs isolated from uterine supernatants of biopsies from obese women (vs. nonobese women) presented a molecular signature focused on cell remodeling and angiogenesis. Lastly, the results of functional assays indicated that supplementation of the culture medium with EVs from nonobese women can rescue (at least in part) the defect in in vitro decidualization described in ESCs from obese women. Lastly, the addition of endometrial EVs from obese women (vs. nonobese women) was associated with significantly greater invasive activity by HTR-8/SVneo cells. In conclusion, our results provided new insights into the endometrial EVs’ pivotal role in the poor uterine receptivity observed in obese women.
2023-10-09 | PXD039568 | Pride