Integrated Single-Cell and Spatial Transcriptomics Reveal Androgen-Driven Disruptions in PCOS Ovarian Microenvironment
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ABSTRACT:
PROVIDER: PRJNA1119462 | ENA |
REPOSITORIES: ENA
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Project description:Polycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder with hyperandrogenemia and impaired follicular development. Granulosa cells (GC) and thecal cells (TC) are crucial during follicular development, but their responses to androgen remain poorly understood at subpopulation levels. Using single-cell RNA sequencing and spatial transcriptomics, we analyzed GC and TC subpopulations in Dehydroepiandrosterone-induced PCOS-like mice to determine the ovarian microenvironment characters. We observed gene expression changes in steroidogenesis and cell-cell communications, with significant landscape shifts in subtypes. GC subsets showed an inflammatory GC5 expansion and loss of luteinized GC7, while TC subsets exhibited an increased TC2 population with enhanced lipid metabolism and androgen response. Intercellular signaling was heightened, particularly with amplified ligand-receptor interactions for Ptn-Ncl and Mdk-Ncl. Steroidogenesis was altered for PCOS's steroid hormone abnormalities. These findings revealed androgen impact in the cell subpopulations of follicular microenvironment and underscored the importance of Ptn-Ncl and Mdk-Ncl in PCOS-associated impaired follicular development.
2024-10-23 | GSE268919 | GEO
Project description:This study reports that high androgen level via perturbation of circadian system modulates liver metabolism and contributes to the development of NAFLD in PCOS conditions.
2022-03-05 | GSE197765 | GEO
Project description:Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production, arrested follicle development, and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. To examine whether the perturbations in follicle growth and the intrafollicular environment affects development of the mature PCOS oocyte, genes that are differentially expressed in PCOS compared to normal oocytes were defined using microarray analysis. This analysis detected approximately 8000 transcripts. Hierarchical clustering and principal component analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. 374 genes had a statistically-significant increase or decrease in mRNA abundance in PCOS oocytes. A subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis, suggesting that increased mRNAs for these proteins may negatively affect oocyte maturation and/or early embryonic development. Of the 374 differentially expressed genes, 68 contained putative androgen receptor, retinoic acid receptor, and/or peroxisome proliferating receptor gamma binding sites, including 9 of the genes involved in chromosome alignment and segregation. These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Furthermore, altered mRNA levels in the PCOS oocyte may contribute to defects in meiosis and/or mitosis which might impair oocyte competence for early development and therefore contribute to poor pregnancy outcome in PCOS. Keywords: disease state analysis
2007-06-05 | GSE5850 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, characterised by elevated circulating androgens and increased expression of androgen receptor (AR) and by downregulation of Wilms Tumour 1 in the endometrium, The objectives of this study are: 1) Understand the functional role of WT1 in regulating decidualization response in healthy endometrial tissue, and 2) understand how interactions between aberrant WT1 and AR expression in PCOS patients result in dysregulation of deciduallization processes
2024-02-16 | GSE240055 | GEO
Project description:In the present study through TLDA analysis we looked into the miRNA differential expression in peripheral blood of PCOS patients v/s control women. The results implicated that many signalling networks as MAPK pathway, Androgen signaling, Insulin signaling and Immune signaling are regulated in peripheral blood of PCOS patients. The data indicate that there is generic PCOS specific gene expression in peripheral blood of PCOS subjects which can reflect the same from other PCO tissues. Total RNA was extracted from peripheral blood of 4 PCOS patients and 4 control subjects and compared for miRNA diferential expression through TLDA
2022-12-31 | GSE54249 | GEO
Project description:In the present study through microarray analysis we looked into the mRNA differential expression in peripheral blood of PCOS patients v/s control women. The results implicated that many signalling networks as MAPK pathway, Androgen signaling, Insulin signaling and Immune signaling are regulated in peripheral blood of PCOS patients. The data indicate that there is generic PCOS specific gene expression in peripheral blood of PCOS subjects which can reflect the same from other PCO tissues. Total RNA was extracted from peripheral blood of 4 PCOS patients and 4 control subjects and compared for mRNA diferential expression through microarray.
2022-12-31 | GSE54248 | GEO
Project description:To reveal microRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Affymetrix miRNA 2.0. Six pooled RNAs from CC samples (three PCOS and three non-PCOS pooled RNAs) were separately analyzed on 6 GeneChip miRNA 2.0 Array (miRBase V15)
2015-04-28 | E-GEOD-68285 | biostudies-arrayexpress
Project description:To reveal mRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. mRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Illumina Novaseq 6000.
2024-10-30 | GSE277906 | GEO
Project description:To reveal microRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Affymetrix miRNA 2.0.
2015-04-28 | GSE68285 | GEO
Project description:Abundant evidence suggests that women with polycystic ovary syndrome (PCOS) have increased metabolic aberrations and cardiovascular risks and present with signs of endothelial cell (EC) dysfunction. However, whether and how androgen is involved in the pathogenesis of EC dysfunction in PCOS remains unclear. Induced pluripotent stem cells (iPSCs) were established in two PCOS patients and two control participants and further differentiated into ECs via monoculture under chemically defined conditions. Both PCOS patients were phenotype A (present with oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology) and were diagnosed with metabolic syndrome. Single-cell transcriptomic analysis of the iPSC-derived ECs revealed functional differences involving the cell cycle process, vascular endothelial growth factor (VEGF) signaling and apoptosis between the PCOS and control groups. Decreased expression of cell proliferation and cell cycle related genes were noted in the PCOS iPSC-derived ECs. Dihydrotestosterone (DHT) treatment significantly enhanced cell proliferation and angiogenic function in the control iPSC-derived ECs. In contrast, significantly deteriorated cell proliferation accompanied with diminished expression of androgen receptor/cyclin-dependent kinase 1/VEGF signaling pathway was shown in the PCOS iPSC-derived ECs after DHT treatment, alongside with impaired angiogenesis demonstrated by the tube formation and wound healing assay. In conclusion, disease-specific iPSCs were successfully established in phenotype A PCOS patients with metabolic syndrome and served as an effective platform for disease modeling in this specific subgroup. Both intrinsic and androgen-induced cellular proliferation and angiogenesis were significantly impaired in the PCOS iPSC-derived ECs, providing new pathogenic evidence for androgen-mediated EC dysfunction and possibly further cardiovascular consequences.
2023-11-01 | GSE246456 | GEO