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Steroid Receptor Coactivator-2 Controls Human Extravillous Trophoblast Cell Proliferation, Migration, and Invasion

ABSTRACT: Steroid Receptor Coactivator-2 Controls Human Extravillous Trophoblast Cell Proliferation, Migration, and Invasion

PROVIDER: PRJNA1168193 | ENA |

REPOSITORIES: ENA

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Steroid Receptor Coactivator-2 Controls Human Extravillous Trophoblast Cell Proliferation, Migration, and Invasion

Project description:Abnormal placentation is a fundamental cause of pregnancy complications including preeclampsia, miscarriage, and intrauterine growth restriction. Proliferation, differentiation, migration, and invasion are key properties of trophoblast cells that regulate trophoblast functions. Imbalance of these cellular processes is linked to placental pathologies. Using HTR-8/SVneo immortalized human trophoblast cells, we demonstrate that steroid receptor coactivator-2 (SRC-2), a transcriptional regulator of nuclear receptors, is essential for extravillous trophoblast cell proliferation, migration, and invasion. Genome-wide transcriptomics identified an SRC-2–dependent transcriptome in HTR-8/SVneo cells that includes a diverse spectrum of proteins involved in placental tissue development and function. To emphasize the utility of this transcriptomics data set, we demonstrate that WNT family member 9A (WNT9A) is not only a molecular target of SRC-2 but also crucial for maintaining many of the cellular properties of human extravillous trophoblast cells.

2025-07-29 | GSE278677 | GEO

Aquaporin 3 promotes human extravillous trophoblast migration and invasion.

Project description:ProblemDoes aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells?Method of studyA lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis.ResultsCompared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown.ConclusionsAQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.

| S-EPMC8006384 | biostudies-literature

Preeclampsia is associated with reduced ISG15 levels impairing extravillous trophoblast invasion.

Project description:Preeclampsia is associated with reduced ISG15 levels impairing extravillous trophoblast invasion.

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Steroid Receptor Coactivator-2 Regulated Transcriptome in Human Endometrial Stromal Cells

Project description:RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of steroid receptor coactivator-2/nuclear receptor coactivator 2 (SRC-2/NCOA2)

2018-10-23 | GSE121584 | GEO

GDF-11 stimulates human extravillous trophoblast cell invasion by upregulating ANGPTL4 expression

Project description:Proper regulation of extravillous trophoblast (EVT) cell invasion is critical for normal placental development and function. Growth differentiation factor 11 (GDF-11), a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to promote EVT cell invasion, yet the underlying molecular mechanisms remain largely unclear. In this study, RNA sequencing identified angiopoietin-like 4 (ANGPTL4), a multifunctional secreted protein, as a novel downstream target of GDF-11. In vitro experiments demonstrated that GDF-11 significantly upregulated ANGPTL4 expression in both HTR-8/SVneo cells and primary human EVT cells. Mechanistically, we found that the type I TGF-β receptors ALK4 and ALK5 were essential for mediating the stimulatory effect of GDF-11 on ANGPTL4 expression. Further analysis revealed that SMAD3, but not SMAD2, was the key transcription factor involved in this process. Using both loss- and gain-of-function approaches, we demonstrated that ANGPTL4 was required for GDF-11-induced EVT cell invasion. Importantly, serum levels of GDF-11 were markedly reduced in patients with preeclampsia (PE), a pregnancy disorder associated with shallow trophoblast invasion and poor placentation. Together, our findings uncover a previously unrecognized GDF-11-ANGPTL4 signaling axis that regulates EVT cell invasion and provide new insight into the pathophysiology of PE.

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2018-12-25 | GSE109682 | GEO

Role of YAP/TAZ-TEAD in human trophoblast

Project description:During placentation, placental cytotrophoblast cells differentiate into syncytiotrophoblast cells and extravillous trophoblast cells. In placenta, the expression of various genes is regulated by the Hippo pathway through the transcriptional coactivator YAP/TAZ-TEAD activity. To examine the effect of YAP/TAZ and/or TEAD on trophoblast differentiation, knockdown experiments were performed. Microarray analysis were performed to identify YAP/TAZ and/or TEAD target genes in human trophoblast.

2022-07-17 | GSE182900 | GEO

GDF-11 stimulates human extravillous trophoblast cell invasion by upregulating ANGPTL4 expression

Project description:GDF-11 stimulates human extravillous trophoblast cell invasion by upregulating ANGPTL4 expression

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A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

Project description:A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

2020-09-06 | GSE157542 | GEO