Differential genes in adipocytes induced from polycystic ovary syndrome-derived and non- polycystic ovary syndrome-derived human embryonic stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52422 | GEO | 2013/11/22
SECONDARY ACCESSION(S): PRJNA229560
REPOSITORIES: GEO
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Project description:To explore the molecular mechanisms of obesity and insulin resistance in the patients with polycystic ovary syndrome (PCOS) at the level of human embryonic stem cells (hESCs).Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.There were 153 differential genes. Of the 153 genes, 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and GeneChip software system indicated that it was associated with obesity and diabetes. Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.
2013-11-22 | E-GEOD-52422 | biostudies-arrayexpress
Project description:Polycystic ovary syndrome (PCOS) is a female endocrine disorder characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. PCOS is often accompanied by symptoms such as insulin resistance, abdominal obesity, and chronic inflammation. Adipose tissue is a crucial endocrine organ involved in metabolic disorders. Metabolic issues and chronic inflammation in PCOS are linked to dysfunctional adipose tissue. Mesenchymal progenitor cells (MPCs) are the precursor cells of adipocytes and can regulate the immune system. In this study, we used induced pluripotent stem cells (iPSCs) from patients with PCOS to derive MPCs and compare the transcriptome profiles between PCOS and HC iPSC-derived MPCs. We also challenged iPSC-derived MPCs with testosterone to assess the impact of androgen on MPCs. We found that 1026 genes differed between PCOS and HC iPSC-derived MPCs. Gene set enrichment analysis showed adipogenesis and metabolic function were reduced, but the inflammatory response was raised in PCOS iPSC-derived MPCs. The critical signals for early adipogenesis, including TGFβ, BMP, WNT, and CEBPA, differed between PCOS and HC iPSC-derived MPCs. After adipogenic induction, mature adipocytes were lower in PCOS iPSC-derived MPCs than HC. Lipolysis, the process involved in fat metabolism, was lower in adipocytes derived from PCOS MPCs than in HC. The testosterone treatment results indicated that genes related to oxidative phosphorylation and fatty acid metabolism were upregulated in HC iPSC-derived MPCs but downregulated in PCOS iPSC-derived MPCs. Short-term androgen stimulation may benefit body functions in HC. The impact of testosterone varied among individuals with HC and PCOS, possibly because of a genetic tendency towards PCOS. This study explains important factors that help us understand PCOS.
2024-08-16 | GSE267287 | GEO
Project description:The effects of how obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring are unclear. We found that daughters of PCOS mothers are more likely to be diagnosed with PCOS in a Swedish nationwide register-based cohort and a clinical case-control study from Chile. Further, female mice (F0) with PCOS-like traits induced by late gestation injection of dihydrotestosterone, with and without obesity, produced female F1–F3 offspring with a PCOS-like reproductive and metabolic phenotypes. Sequencing of single MII oocytes from F1–F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of PCOS mothers and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
2019-10-30 | GSE133100 | GEO
Project description:CONTEXT: The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of the syndrome. OBJECTIVE: The objective was to study the expression profiles of omental fat biopsy samples obtained from morbidly obese women with or without PCOS at the time of bariatric surgery. DESIGN: This was a case-control study. SETTINGS: We conducted the study in an academic hospital. PATIENTS: Eight PCOS patients and seven nonhyperandrogenic women submitted to bariatric surgery because of morbid obesity. INTERVENTIONS: Biopsy samples of omental fat were obtained during bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was high-density oligonucleotide arrays. RESULTS: After statistical analysis, we identified changes in the expression patterns of 63 genes between PCOS and control samples. Gene classification was assessed through data mining of Gene Ontology annotations and cluster analysis of dysregulated genes between both groups. These methods highlighted abnormal expression of genes encoding certain components of several biological pathways related to insulin signaling and Wnt signaling, oxidative stress, inflammation, immune function, and lipid metabolism, as well as other genes previously related to PCOS or to the metabolic syndrome. CONCLUSION: The differences in the gene expression profiles in visceral adipose tissue of PCOS patients compared with nonhyperandrogenic women involve multiple genes related to several biological pathways, suggesting that the involvement of abdominal obesity in the pathogenesis of PCOS is more ample than previously thought and is not restricted to the induction of insulin resistance.
2007-10-26 | E-GEOD-5090 | biostudies-arrayexpress
Project description:Obesity has been linked with a host of metabolic and reproductive disorders including polycystic ovary syndrome (PCOS). While a distinct link exists between obesity and PCOS, the exact pathogenesis of the disease remains less understood and limited research has explored the impact of diet on the development of PCOS. With the primary symptoms of PCOS including hyperandrogenism, anovulation, and polycystic ovaries, most animal models utilize androgen treatment to effectively induce PCOS. However, these models fail to address the underlying causes of disease symptoms and do not effectively demonstrate the metabolic features of the disease such as hyperinsulinemia. Here, we present a novel rodent model of diet-induced obesity that recapitulates both the metabolic and reproductive phenotypes of human PCOS. In utilizing a high-fat high-sugar (HFHS) diet, we have created a model of PCOS that allows for the study of metabolic parameters and their impact on ovarian follicle development and reproductive health. Animals on the HFHS diet not only demonstrated signs of metabolic impairment, but they also developed polycystic ovaries and experienced irregular estrous cycling marked by an extended period spent in estrus. Though hyperandrogenism was not characteristic of HFHS diet animals as a group, testosterone levels were predictive of a polycystic ovarian morphology. Importantly, PCOS was induced similarly to the disease etiology in humans, allowing this model to offer the unique opportunity to study PCOS at its genesis rather than following the development of disease symptoms.
2017-06-01 | GSE83220 | 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. Experiment Overall Design: A single MII oocyte, defined by one polar body in the perivitelline space and no visible nuclear structure in the cytoplasm, was collected from 6 individual NL and 6 individual PCOS ovaries, placed immediately in TRIzol (Sigma, St. Louis MO), and stored at -80 C until further study. Total RNA was isolated from each oocyte and subjected to three rounds of linear amplification with the Ovation Biotin RNA Amplification and Labeling System (NuGen Technologies, San Carlos CA) per the manufacturerâs instructions. RNA from the GeneChip Eukaryotic Poly-A RNA Control Kit (Affymetrix, Santa Clara CA) was amplified and labeled under the same conditions for a positive control. Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray chips (Affymetrix, Santa Clara, CA) were hybridized at the University of Pennsylvania Microarray Core Facility. Briefly, the linear-amplified, biotin-labled cDNA from 6 NL (N1-N6) and 6 PCOS (P1-P6) oocytes was hybridized to individual Affymetrix U133 chips. The fluorescence intensity of each chip was normalized to a trimmed mean signal of 150. Each transcript on the U133 chip was defined as present or absent in each oocyte sample using the Affymetrix Microarray Suite 5.0.
2008-06-14 | E-GEOD-5850 | biostudies-arrayexpress
Project description:Obese or polycystic ovary syndrome (PCOS) women have encountered poor reproductive outcomes in natural as well as assisted conception. Furthermore, pregnancy complications of women with PCOS are profoundly worsened by obesity. Both obesity and PCOS affect function of granulosa cells, which is essential in offering the oocyte with nutrients and growth regulators.
2021-04-14 | GSE80432 | GEO
Project description:Exosomes have recently been shown to play a key role in cell-to-cell communication through delivery of various functional content, including microRNAs (miRNAs). We investigated the potential roles of exosomal miRNA derived intrafollicular cells in polycystic ovary syndrome (PCOS). Using microarray profiling, a total of 492 miRNAs and 220 miRNAs were found in follicular fluid-derived exosomes and serum-derived exosomes, respectively, in PCOS and non-PCOS females. By excluding miRNAs existing in serum-derived exosomes, we found 179 miRNAs which were specifically expressed in follicular fluid-derived exosomes both in PCOS and non-PCOS females. Using microarray profiling, a total of 492 miRNAs and 220 miRNAs were found in follicular fluid-derived exosomes and serum-derived exosomes, respectively, in PCOS and non-PCOS females. By excluding miRNAs existing in serum-derived exosomes, we found 179 miRNAs which were specifically expressed in follicular fluid-derived exosomes both in PCOS and non-PCOS females.
2022-02-01 | GSE145318 | GEO
Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disease in reproductive-aged women, is associated with an increased prevalence and extent of coronary artery disease. However, the underlying mechanism remains unclear. Here, we observed that hearts from PCOS mice were characterized by increased total macrophage accumulation. Monocyte-derived macrophages were significantly increased in the hearts of PCOS mice owing to enhanced circulating monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Compared with non-PCOS animals, PCOS-induced mice showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional Vcam1 silencing in PCOS mice significantly suppressed cardiac inflammation and improved post-MI cardiac injury. Our data documented new mechanisms through which PCOS may affect cardiovascular health in women.
2024-01-02 | GSE238074 | GEO
Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disease in reproductive-aged women, is associated with an increased prevalence and extent of coronary artery disease. However, the underlying mechanism remains unclear. Here, we observed that hearts from PCOS mice were characterized by increased total macrophage accumulation. Monocyte-derived macrophages were significantly increased in the hearts of PCOS mice owing to enhanced circulating monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Compared with non-PCOS animals, PCOS-induced mice showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional Vcam1 silencing in PCOS mice significantly suppressed cardiac inflammation and improved post-MI cardiac injury. Our data documented new mechanisms through which PCOS may affect cardiovascular health in women.
2024-01-02 | GSE238073 | GEO