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Circulating resistin and follistatin levels in obese and non-obese women with polycystic ovary syndrome: A systematic review and meta-analysis.

ABSTRACT: This meta-analysis was performed to resolve the inconsistencies regarding resistin and follistatin levels in women with polycystic ovary syndrome (PCOS) by pooling the available evidence. A systematic literature search using PubMed and Scopus was carried out through November 2020 to obtain all pertinent studies. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between the levels of resistin and follistatin with PCOS in the overall and stratified analysis by obesity status. A total of 47 publications, 38 for resistin (2424 cases; 1906 controls) and 9 studies for follistatin (815 cases; 328 controls), were included in the meta-analysis. Resistin levels were significantly higher in PCOS women compared with non-PCOS controls (WMD = 1.96 ng/ml; 95%CI = 1.25-2.67, P≤0.001) as well as in obese PCOS women vs. obese controls, and in non-obese PCOS women compared with non-obese controls, but not in obese PCOS vs. non-obese PCOS patients,. A significantly increased circulating follistatin was found in PCOS patients compared with the controls (WMD = 0.44 ng/ml; 95%CI = 0.30-0.58, P≤0.001) and in non-obese PCOS women compared with non-obese controls and in obese PCOS women vs. obese controls, but, no significant difference in follistatin level was observed in obese PCOS compared with non-obese PCOS women. Significant heterogeneity and publication bias was evident for some analyses. Circulating levels of resistin and follistatin, independent of obesity status, are higher in women with PCOS compared with controls, showing that these adipokines may contribute to the pathology of PCOS.

SUBMITTER: Raeisi T

PROVIDER: S-EPMC7978365 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPolychlorinated biphenyls (PCBs), organic lipophilic pollutants that accumulate through diet and increase with age, have been associated with polycystic ovary syndrome (PCOS) and shown to affect microRNA (miRNA) expression. This work aimed to determine if PCBs were associated with circulating miRNAs and whether there were any correlations with serum PCB/miRNA levels and hormonal changes.Methods29 non-obese PCOS and 29 healthy control women, with similar age and body mass index (BMI), had their serum miRNAs measured together with 7 indicator PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, PCB180) using high resolution gas chromatography coupled with high resolution mass spectrometry.ResultsIn the combined study cohort, four miRNAs (hsa-miR-139-5p, hsa-miR-424-5p, hsa-miR-195-5p, hsa-miR-335-5p) correlated with PCBs, but none correlated with metabolic parameters. hsa-miR-335-5p correlated with FSH. When stratified, 25 miRNAs correlated with PCBs in controls compared to only one (hsa-miR-193a-5p) in PCOS; none of these miRNAs correlated with the metabolic parameters of BMI, insulin resistance, or inflammation (C-reactive protein, CRP). However, of these 25 miRNAs in controls, hsa-miR-26a-5p, hsa-miR-193a-5p, hsa-miR-2110 and hsa-miR-195-5p positively correlated with luteinizing hormone (LH), hsa-miR-99b-5p and hsa-miR-146b-5p correlated with estradiol, hsa-miR-193a-5p correlated with progesterone, hsa-miR-195-5p correlated with follicle stimulating hormone (FSH), and hsa-miR-139-5p and hsa-miR-146b-5p negatively correlated with anti-müllerian hormone (AMH) (all p<0.05). hsa-miR-193a-5p in PCOS cases correlated with estradiol.ConclusionIn this cohort of women, with no difference in age and BMI, and with similar PCB levels, the miRNAs correlating to PCBs associated with menstrual cycle factors in healthy menstruating controls versus the anovulatory PCOS subjects. The PCB-associated miRNAs did not correlate with non-reproductive hormonal and metabolic parameters. This suggests that PCB effects on miRNAs may result in changes to the hypothalamo-ovarian axis that may thus affect fertility.

Project description:BACKGROUND:Women with Polycystic Ovary Syndrome (PCOS) present a heterogeneous reproductive and metabolic profile with an increased lifetime risk of Type 2 Diabetes (T2D). Early biomarkers of these metabolic disturbances in PCOS women have not been identified. The abundance of circulating insulin gene promotor cell-free DNA (INS cfDNA) was shown to be valuable as a predictive biomarker of ?-cell death in individuals with Type 1 diabetes (T1D) as well as with gestational diabetes. Since ?-cell death is common to the development of T1D as well as in T2D, we aimed to investigate if insulin-coding DNA is more abundant in circulation of PCOS women (vs Controls) and if their levels change after 6?yr. follow-up as a potential measure to predict future T2D. METHODS:A cohort of 40 women diagnosed with PCOS according to Rotterdam 2003 criteria and eight healthy controls were examined at baseline and 6?years follow-up. Clinical measurements for evaluation of glucose homeostasis as well as blood/serum samples were obtained at each visit. Methylated and unmethylated INS cfDNA were quantified using droplet digital PCR. Differences between groups were assessed using Kruskall-Wallis test and Wilcoxon Signed rank test. RESULTS:At baseline, there was no detectable difference in copy number (copies/?L) of methylated (p =?0.74) or unmethylated INS cfDNA (p =?0.34) between PCOS and Control groups. At follow up, neither methylated (p =?0.50) nor unmethylated INScfDNA levels (p =?0.48) differed significantly between these groups. Likewise, when pooling the groups, there was no difference between baseline and follow up, in terms of copies of methylated or unmethylated INS cfDNA (p =?0.38 and p =?0.52, respectively). There were no significant correlations between counts of unmethylated or methylated cfDNA and the clinical measurements of ?-cell function and pre-diabetes. CONCLUSION:The circulating level of unmethylated and methylated INScfDNA is similar between PCOS and Controls and cannot be used to predict islet ?-cell loss and progression to Type 2 diabetes in a 6-year follow-up. TRIAL REGISTRATION:The Danish Data Protection Agency (REG-31-2016. Approval: 01-12-2015) and by the Danish Scientific Ethical committee of Region Zealand (Journal no. SJ-525. Approval: 13-06-2016), Clinicaltrials.gov, ( NCT03142633 , registered 1. March, 2017, Retrospectively registered).

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Circulating resistin and follistatin levels in obese and non-obese women with polycystic ovary syndrome: A systematic review and meta-analysis.

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