Dataset Information

Differential Lipidomic Characteristics of Children Born to Women with Polycystic Ovary Syndrome.

ABSTRACT:

Objective

To describe the lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS) women (PCOS-off) and assess the associations between differential lipids and clinical phenotypes.

Methods

Ultra performance liquid chromatography and mass spectrometry were performed on plasma samples from 70 PCOS-off and 71 healthy controls. The associations of differential metabolites with clinical phenotypes were examined by multiple linear regression.

Results

Forty-four metabolites were significantly altered in PCOS-off, including 8 increased and 36 decreased. After stratification according to sex, 44 metabolites (13 increased and 31 decreased) were expressed differently in girls born to PCOS women (PCOS-g), most of which were glycerolipids. Furthermore, 46 metabolites (9 increased and 35 decreased) were expressed differently in boys born to PCOS women (PCOS-b), most of which were glycerophospholipids. Significant associations of metabolites with weight Z-score and high density lipoprotein cholesterol were found in PCOS-off. Triglycerides, low density lipoprotein cholesterol, and thyroid-stimulating hormone were separately correlated with some lipids in PCOS-g and PCOS-b.

Conclusions

PCOS-off showed specific lipid profile alterations. The abnormal level of glycerophospholipids and sphingomyelin indicated the risk of glucose metabolism and cardiovascular diseases in PCOS-off. Some lipids, such as phosphatidylcholines, lysophosphatidylcholine and sphingomyelin, may be the potential markers. The results broadened our understanding of PCOS-offs' cardiometabolic status and emphasized more specific and detailed monitoring and management in this population.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC8380809 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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: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.

Project description:BackgroundPolycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.ObjectivesTo assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.Search methodsWe searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.Selection criteriaRandomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.Data collection and analysisTwo authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).Main resultsWe included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence).Authors' conclusionsLifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.