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New insights into the genic and metabolic characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.

ABSTRACT: BACKGROUND:Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects female fertility. However, with the lack of a corresponding research model, the pathology mechanism of PCOS is poorly understood. Induced pluripotent stem cell (iPSC) technology has been recognized as means to generate patient-specific stem cells for disease modeling. METHODS:The mRNA abundance of iPSCs was analyzed by RNA microarray and real-time polymerase chain reaction (RT-PCR). Karyotyping of iPSCs was performed with cytogenetic analysis. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XF extracellular flux analyzer. The expression of iPSC-associated markers was identified by immunofluorescence and RT-PCR. The teratoma formation of iPSCs was studied using immunochemistry. RESULTS:A PCOS patient-derived iPSC model was established from somatic cells of PCOS patients. Through comprehensive transcriptional profiling analysis of the RNA microarray, PCOS patient-derived iPSCs showed metabolic abnormalities and mitochondrial dysfunction compared with non-PCOS patient-derived iPSCs in vitro?. Specifically, a total of 2904 genes were differentially expressed between the two iPSC populations, of which 1416 genes were upregulated and 1488 genes were downregulated (fold change >?2, p?

SUBMITTER: Min Z

PROVIDER: S-EPMC6085636 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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New insights into the genic and metabolic characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.

Min Zheying Z Gao Qian Q Zhen Xiumei X Fan Yong Y Tan Tao T Li Rong R Zhao Yue Y Yu Yang Y

Stem cell research & therapy 20180809 1

<h4>Background</h4>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects female fertility. However, with the lack of a corresponding research model, the pathology mechanism of PCOS is poorly understood. Induced pluripotent stem cell (iPSC) technology has been recognized as means to generate patient-specific stem cells for disease modeling.<h4>Methods</h4>The mRNA abundance of iPSCs was analyzed by RNA microarray and real-time polymerase chain reaction (RT-PCR ...[more]

PMID: 30092830

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Project description:BackgroundPolycystic ovary syndrome (PCOS) is a kind of endocrine and metabolic disorder, disturbing the females of reproductive age. Here, we aimed to investigate the metabolic characteristics of overweight women with PCOS and analyze the possible mechanisms.MethodsWe conducted a cross-sectional study on 947 patients with PCOS, who were classified according to body mass index (BMI) as overweight (BMI ≥ 24 kg/m2) or non-overweight (BMI ≤ 23.9 kg/m2). The clinical symptoms, endocrine features, metabolic status, and inflammatory levels of the patients were comprehensively assessed and compared between the patients of the two groups. Additionally, a predictive study on the correlation between inflammation and metabolism was performed using STRING and Cytoscape software, and the possible mechanisms of metabolic disorders involved in the overweight PCOS were preliminarily explored.ResultsOverweight PCOS was associated with increased average age, waist-to-hip ratio, and the incidence of acanthosis nigricans. These patients were susceptible to familial hypertension and diabetes, and exhibited evident characteristics of low levels of luteinizing hormone (LH) and the ratio of LH to follicle-stimulating hormone, and were more inclined to insulin resistance (IR). Furthermore, overweight PCOS presented with a chronic low-grade inflammation state with increased levels of inflammatory cytokines complement components C5/C5α, CXCL12/SDF-1, MIF, and Serpin E1/PAI-1 evidently compared with those in non-overweight PCOS. Pearson analysis showed that these inflammatory cytokines were directly or indirectly correlated with IR. The STRING and Cytoscape network analysis predicted that inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1 and MIF might be crucial for inducing IR in overweight PCOS women through various biological functions and signal transductions including the JAK-STAT cascade, ATP biosynthesis, and HIF-1 signaling.ConclusionsOverweight patients with PCOS are prone to low gonadal levels, IR, and chronic low-grade inflammation. Inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1and MIF might lead to IR through multiple biological functions and signal transductions in overweight PCOS.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is an endocrine disorder that commonly affects women of childbearing age and has been associated with metabolic and reproductive abnormalities. Only a few studies have investigated metabolic traits in women with PCOS in Latin America. Therefore, we conducted a systematic review to provide an overview of the available evidence on the metabolic profile of Latin American women with PCOS.MethodsWe searched PubMed, Cochrane Central Register of Controlled Trials, and Embase databases for cross-sectional, case-control, or cohort studies focusing on populations of countries in South and Central America and Mexico, published until October 31, 2019. We selected studies that reported the diagnostic criteria for PCOS. In the absence of a control group, we included studies if they reported relevant metabolic data.ResultsThe initial search yielded 4878 records, of which 41 studies were included in the systematic review. Sample sizes ranged from 10 to 288 in PCOS groups and from 10 to 1500 in control groups. The prevalence of phenotypes A and B (classic PCOS) ranged from 65.8% to 87.5% as reported in studies from Argentina, Brazil, and Chile. Metabolic syndrome ranged from 33.3% to 44.0% for phenotype A, from 15.0% to 58.0% for phenotype B, from 11.9% to 36.0% for phenotype C, and from 14.2% to 66.0% for phenotype D. Women with PCOS had higher body mass index, waist circumference, blood pressure, glucose, and homeostasis model assessment index as well as a more adverse lipid profile than those without PCOS.ConclusionsEvidence from the present systematic review suggests that anthropometric and metabolic profiles are worse in women with PCOS who live in different Latin American countries than in women without PCOS living in the same region. Additional studies assessing metabolic comorbidities, such as diabetes, and distinct PCOS phenotypes in different Latin American countries are warranted and may produce invaluable information for primary and secondary prevention of PCOS in the region. This systematic review was registered with PROSPERO under number CRD42016038537.Systematic review registrationPROSPERO, identifier CRD42016038537.

Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.

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New insights into the genic and metabolic characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.

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New insights into the genic and metabolic characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.

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