Resistance and Aerobic Exercise Intervention Induces Differential DNA Methylation in Women with Polycystic Ovary Syndrome: a clinical trial study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213363 | GEO | 2023/09/08
REPOSITORIES: GEO
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Project description:Polycystic ovary syndrome (PCOS) is characterised by a hormonal imbalance affecting the reproductive and metabolic health of reproductive-aged women. Exercise is often recommended as a first-line therapy for women with PCOS to help improve their overall health however, women with PCOS are resistant to the metabolic benefits of exercise training. Here, we aimed to gain insight into the mechanisms responsible for such resistance to exercise in PCOS. We employed an in vitro approach with electrical pulse stimulation (EPS) of cultured skeletal muscle cells to explore whether muscle cells from women with PCOS have an altered gene expression signature in response to muscle contraction. Following EPS, 4,719 genes were differentially expressed (FDR < 0.05) in myotubes from women with PCOS compared to only 173 in healthy control women. Both groups included genes involved in skeletal muscle contraction. We also determined the effect of two transforming growth factor-beta ligands that are elevated in plasma of women with PCOS, the transforming growth factor beta-1 (TGFβ1) and the anti-müllerian hormone (AMH), alone and on the EPS-induced response. While AMH (30 ng/ml) had no effect, TGFβ1 (5 ng/ml) induced the expression of extracellular matrix genes and impaired the exercise-like gene expression signature in myotubes from women with and without PCOS in response to EPS by interfering with key processes related to muscle contraction, calcium transport and actin filament. Collectively, our findings suggest that while the fundamental gene expression responses of skeletal muscle to contraction is intact in PCOS, elevated circulating factors like TGFβ1 may be responsible for the impaired adaptation to exercise intervention in women with PCOS.
2022-10-12 | GSE199225 | GEO
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. PCOS has been associated with adverse pregnancy outcomes and abnormalities of the placenta. By taking a quantitative label-free quantitative proteomics approach we set out to investigate if changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. We have performed label-free quantitative proteomics on plasma samples from pregnant women with PCOS at term (n=14) and plasma samples from pregnant control women (n = 23) matched for age, gestational length and BMI. The samples are derived from BASIC pregnancy cohort from Uppsala, Sweden. A total of 169 proteins with two or more unique peptides were identified.
2019-11-25 | PXD012034 | Pride
Project description:Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder. Epigenetic etiology is suggested to play an important role in PCOS pathogenesis, since it is hard to elucidate completely by genetic variations. Exosomal microRNAs (miRNAs) have recently been identified as a novel mechanism of intercellular communication, and a more stable regulator of gene expression compared with free miRNAs. The aim of this study is to detect the different expression profile of plasma exosomal miRNAs between PCOS patients and healthy controls.
2021-07-01 | GSE142819 | 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:Our study is based on the hypothesis that PCOS can be explained by an integrated, epigenetic model, whereby environmental factors modify the effect of susceptibility genes and influence the clinical heterogeneity that is characteristic of the syndrome during adult life. With the aim to understand the molecular mechanisms underlying PCOS, we report results from a case-control, genome-wide methylation study using human DNA from granulosa lutein cells.
2019-03-01 | E-MTAB-6672 | biostudies-arrayexpress
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:Lean polycystic ovary syndrome (PCOS) women have a greater proportion of android (abdominal) fat, increased numbers of small subcutaneous (SC) abdominal adipocytes and preferential intra-abdominal fat accumulation. This study examines whether abnormal gene expression of SC abdominal adipose stem cells (ASCs) from lean PCOS women underlies this altered abdominal adipose structure-function. In this dataset, we include the expression data obtained from PCOS and NL subcutaneous adipose tissue. Differential expression of at least 1.5-fold change (P<0.05) were obtained in 120 genes (48 upregulated, 72 downregulated) of SC abdominal ASCs from PCOS versus NL women
2017-05-03 | GSE98421 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a complex endocrinopathy affecting reproductive aged women, whose etiology has not been fully understood yet. The follicular growth is arrested at preantral stage leading to cyst formation, consequently resulting in anovulatory infertility in these women. As follicular fluid provides the microenvironment for the growing oocyte, molecular profiling of the fluid may provide unique information about pathophysiology associated with follicular development in PCOS. Modification with oligosaccharide chains are known to influence functions of several secreted proteins and these glycoproteins also play a role in disease pathology. The glycoproteomic profile of follicular fluid of PCOS has not been explored in PCOS yet. In the present study, we performed comparative glycoproteomic analysis by first enriching glycoproteins using three different lectins viz. concanavalin A, wheat germ agglutinin and Jacalin from follicular fluid of women with PCOS and controls undergoing in vitro fertilization. Peptides generated by trypsin digestion were labeled with isobaric tags for relative and absolute quantification reagents and analyzed by liquid chromatography tandem mass spectrometry. We identified 10 differentially expressed glycoproteins, in the follicular fluid of women with PCOS compared to control. Two important differentially expressed proteins- SERPINA1 and ITIH4, were consistently upregulated and downregulated respectively, upon validation by Western blotting in follicular fluid and real-time polymerase chain reaction in granulosa cells. These proteins play a role in angiogenesis and extracellular matrix stabilization which are vital for follicle maturation. In conclusion, comparative glycoprotein profiling of follicular fluid from women with PCOS and controls revealed altered expression of proteins which may contribute to defects in follicle development in PCOS pathophysiology.
2019-03-22 | PXD012731 | Pride
Project description:Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.
2021-03-08 | GSE168404 | GEO
Project description:In vitro studies of subcutaneous (SC) abdominal adipose stem cells (ASC) from women with polycystic ovary syndrome (PCOS) show altered ASC commitment to preadipocytes and differentiation to mature adipocytes related to hyperandrogenism. The goal of the study is to use microarrays to examine whether SC abdominal ASC gene expression are altered in normal-weight PCOS women and correlated with hyperandrogenemia and/or insulin resistance, which are prevalent clinical pathologies of PCOS.
2019-01-24 | GSE124226 | GEO