Gene regulatory activity associated with PCOS reveals DENND1A-dependent testosterone production
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ABSTRACT:
PROVIDER: PRJNA1091943 | ENA |
REPOSITORIES: ENA
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Project description:Polycystic Ovary Syndrome (PCOS) is a leading cause of infertility. About 5 million women in the US have PCOS, making it the most prevalent endocrine disorder among menstruating people. Despite that prevalence, the underlying causes remain unknown. Genome-wide association studies (GWAS) have identified non-coding genetic variation associated with PCOS risk and identifying the underlying molecular mechanisms is currently a major opportunity for improving diagnosis and treatment. We report the discovery of gene regulatory mechanisms that help explain genetic association with PCOS in the GATA4, FSHB and DENND1A loci. We based those findings using a combination of high throughput reporter assays, CRISPR-based epigenome editing, and genetic association analysis from PCOS case and control populations. In addition, we found that elevated endogenous DENND1A expression causes elevated testosterone levels, a hallmark PCOS phenotype. These results further highlight the potential for combining genetic variant analyses with experimental approaches to fine map genetic associations with disease risk.
2024-03-30 | GSE262471 | 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:We generated scaffold-free endometrial organoids from human primary endometrial tissues. These organoids were subjected to stepwise hormone treatments for 14 days mimicking the proliferative phase of menstrual cycle or with constantly high testosterone mimicking PCOS conditions
2019-12-01 | GSE128328 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease characterized by persistent anovulation and hyperandrogenism, affecting approximately 8%-10% of women of childbearing age and occupying an important position in the etiology of infertility. There is increasing evidence that lncRNAs are involved in the development of PCOS, but the potential regulatory mechanism is still unclear. This study performed high-throughput lncRNA sequencing of follicular fluid exosomes in non-PCOS infertility patients and PCOS infertility patients. The sequencing results led to the identification of 1253 upregulated and 613 downregulated lncRNAs from a total of 1866 detected candidates. There was no significant difference between the PCOS patients and non-PCOS patients in body mass index (BMI) or the fasting blood glucose (FBG) level. However, luteinizing hormone (LH), estradiol (E2), testosterone (T), serum prolactin (PRL) and anti-Mullerian hormone (AMH) levels were clearly upregulated in PCOS patients compared to those in non-PCOS patients. There was also an increase in LH/FSH (>2) in the PCOS patients. Functional analysis showed that the functions of lncRNAs were related to adenine metabolism, adenine biosynthesis and cytidine triphosphate biosynthesis. These results suggest that lncRNAs may play an important role in the pathogenesis of PCOS and may be potential targets for the diagnosis and treatment of PCOS.
2021-03-11 | GSE159466 | GEO
Project description:Prenatal testosterone treated sheep, similar to PCOS women, manifest reduced cyclicity, functional hyperandrogenism and polycystic ovary (PCO) morphology. The PCO morphology results from increased follicular recruitment and persistence of antral follicles, consequence of reduced follicular growth and atresia, and driven by cell-specific gene expression changes that are poorly understood. Therefore, utilizing RNA sequencing, cell-specific transcriptional changes were assessed in laser capture microdissection isolated antral follicular granulosa and theca cells from 21 months-of- age control and prenatal testosterone treated sheep.
2020-06-18 | GSE150236 | 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: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:To identify the altered miRNA expression profiles of PCOS patients, the differentially expressed miRNAs were identified from cumulus cells of PCOS patients by comparing to that of normal women. Case-control study that involved 18 women with PCOS and 18 women without PCOS (control). The miRNA expression profiles of cumulus cells were identified by miRNA array.
2016-06-01 | E-GEOD-72274 | biostudies-arrayexpress
Project description:Developmental Programming: Adipose Depot-Specific Transcriptional Regulation by Prenatal Testosterone Excess in a Sheep Model of PCOS
| PRJNA665223 | ENA