Dataset Information

Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.

ABSTRACT:

Objective

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of Brazilian women with and without PCOS and to evaluate the potential role of miRNAs in the pathophysiology of the syndrome.

Methods

Cross-sectional study of 36 well-characterized PCOS women and 16 healthy controls. Clinical, hormone and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNA selected were analyzed by taqman quantitative real time polymerase chain reactions (RT-PCR) using a customized Open Array platform. Statistical and bioinformatic analyzed were performed.

Results

Circulating miR-21-5p, miR-23a-3p and miR-26a-5p were upregulated, and miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p were downregulated in women with PCOS compared to healthy normo-ovulatory controls. miR-21-5p, miR-103a-3p and miR-376a-3p levels correlated positively with androgen levels. These miRNAs, in combination, were related to pathways involved in insulin signaling, steroids biosynthesis and endothelial regulation as well as in folliculogenesis.

Conclusion

In this study, we identified a specific circulating miRNA signature in Brazilian women with PCOS. According to our data, circulating miR-21-5p, miR-23a-3p, miR-26a-5p, miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p may represent potential candidates for differential diagnosis of PCOS in the future.

SUBMITTER: De Nardo Maffazioli G

PROVIDER: S-EPMC9543946 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.

De Nardo Maffazioli Giovana G Baracat Edmund Chada EC Soares José Maria JM Carvalho Kátia Cândido KC Maciel Gustavo Arantes Rosa GAR

PloS one 20221007 10

<h4>Objective</h4>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of ...[more]

PMID: 36206272

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Project description:BackgroundWomen with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS.Methods and materialsClinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman® Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease.ResultsWomen with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling.ConclusionsThese studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.

Project description:ObjectiveTo investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS.MethodsWe conducted a cross-sectional study of 166 women with PCOS and 139 age-matched control women at Peking University Third Hospital (Beijing, China) from March 2016 to December 2021. All participants underwent bioimpedance rate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, body composition parameters were assessed, based on the methods used in a previous study. Homeostasis model assessment-insulin resistance (HOMA-IR) and other indices calculated from fasting glucose and insulin were used to measure insulin resistance. The hormonal profiles [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), total testosterone (T), and androstenedione (A2)] were assessed by using biochemical methods. Two subgroup analyses were conducted according to waist-to-hip ratio (WHR; < 0.85, non-central obesity and ≥ 0.85, central obesity) and body fat percentage (BFP; < 35% for lean and ≥35% for obesity). The indices above were analyzed using a two-sided t-test or Wilcoxon rank sum test. Linear regression was used to investigate the effects of body composition on metabolism and sex hormones in the PCOS and control groups.ResultsCompared to women without PCOS, women with PCOS and central obesity (P=0.021), PCOS and noncentral obesity (P<0.001), PCOS and high BFP (P<0.001), and PCOS and low BFP (P<0.001) had more severe glucose metabolism evaluated with HOMA-IR. Women with PCOS experienced greater insulin sensitivity impairment than did the normal population for every equal increase in BFP. LH, LH/FSH, total testosterone, and androstenedione were significantly higher in patients with PCOS than in healthy controls, regardless of WHR and BFP stratification. However, negative correlations existed between body fat indices (i.e., BFP and body mass index) and hormone indices (i.e., LH and androstenedione) in the PCOS group, but were absent in the control group.ConclusionsObese and non-obese women with PCOS have more severe insulin resistance and sex-hormone disorders than women without PCOS. The effect of body fat on sex-hormone disorders is only exist in women with PCOS. These findings suggested that PCOS clinical guidelines should be more specific to body fat.Clinical trial registrationhttps://clinicaltrials.gov/, Registration No. NCT04264832.

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.

Dataset Information

Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.

Objective

Methods

Results

Conclusion

Publications

Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.

Similar Datasets

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