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Androgen-mediated perturbation of hepatic circadian system through epigenetic modulation promotes NAFLD in PCOS mice

ABSTRACT: Androgen-mediated perturbation of hepatic circadian system through epigenetic modulation promotes NAFLD in PCOS mice

PROVIDER: PRJNA812011 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18229815_1.fastq.gz	Fastqsanger.gz
	SRR18229815_2.fastq.gz	Fastqsanger.gz
	SRR18229816_1.fastq.gz	Fastqsanger.gz
	SRR18229816_2.fastq.gz	Fastqsanger.gz
	SRR18229817_1.fastq.gz	Fastqsanger.gz

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Androgen-mediated perturbation of hepatic circadian system through epigenetic modulation promotes NAFLD in PCOS mice

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

Androgen-mediated Perturbation of the Hepatic Circadian System Through Epigenetic Modulation Promotes NAFLD in PCOS Mice.

Project description:In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS.

| S-EPMC9419696 | biostudies-literature

Integrated Single-Cell and Spatial Transcriptomics Reveal Androgen-Driven Disruptions in PCOS Ovarian Microenvironment

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

Microarray analysis of NL and PCOS oocytes

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

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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

TLDA miRNA expression profiling of peripheral blood samples in PCOS patients

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

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Microarray mRNA expression profiling of peripheral blood samples in PCOS patients

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

miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS

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

Transcriptional analysis reveals the progression of PCOS to ovarian cancer in medaka fish ancestrally exposed to BPA

Project description:As a heterogeneous reproductive disorder with unclear etiopathogenesis, polycystic ovary syndrome (PCOS) can be caused by genetic, diet, and environmental factors. Bisphenol A (BPA), a global environmental contaminant, can induce PCOS and NAFLD due to direct exposure; however, whether these phenotypes persist in future unexposed generations is not currently understood. We observed genes abnormally expressed in the ovary of BPA lineage, similar to human PCOS patients. IPA analyses revealed activation of the cancerous pathway, arginine-proline metabolism, insulin signaling, AMPK, and HOTAIR regulatory pathways, as well as upstream regulators esr1 and tgf β.

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miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS

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