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Gene Expression Data of Adipose Stem Cells from Normal-Weight Polycystic Ovary Syndrome Women vs. Controls

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124226 | GEO | 2019/01/24

REPOSITORIES: GEO

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Expression data from subcutaneous adipose tissue of lean polycystic ovary syndrome (PCOS) and normoandrogenic women

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Project description:Polycystic ovary syndrome (PCOS) is a heterogeneous condition, of polyhedric pathogenesis and clinical presentation, defined by oligo-/anovulation, hyperandrogenism and/or polycystic ovaries. Metabolic complications are highly common also in patients suffering PCOS, including obesity, insulin resistance and type-2 diabetes, which severely compromise the clinical course of affected women. Yet, therapeutic options for PCOS remain mostly symptomatic and of limited efficacy for improving both metabolic and reproductive alterations. We report herein the hormonal, metabolic and gonadal responses to different GLP1-based multi-agonists, namely GLP1/Estrogen (GLP1/E), GLP1/GIP and GLP1/GIP/Glucagon, in two murine models of PCOS, with variable penetrance of metabolic and reproductive traits, and their comparison with metformin. Our data illustrate the superior efficacy of the di-agonist, GLP1/E, vs. other multi-agonists and metformin in the management of the metabolic complications of PCOS; GLP1/E was able to ameliorate also ovarian cyclicity in an ovulatory model of PCOS, without direct estrogenic uterotrophic effects. In keeping with GLP1-mediated brain targeting, label-free, quantitative proteomics revealed changes in common and distinct hypothalamic pathways in response to GLP1/E between the two PCOS models, as basis for differential efficiency. Altogether, our data set the basis for the use of GLP1-based multi-agonists, and particularly GLP1/E, in the personalized management of PCOS.

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Project description:Context: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive- aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions:GCcytokine/chemokinemRNAswere identified and analyzed by gene-chip microarrays/ qPCR before and after culture withhumanchorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.

2017-08-07 | GSE102293 | GEO

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