Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome.

Anja E Sørensen,Grzegorz Maciag,Guozhi Jiang,Negar Saliani,Louise T Dalgaard,Anandwardhan A Hardikar,Marie Louise M Wissing,Andrzej S Januszewski,Ronald C Ma,Anne Lis M Englund,Julian Geiger,Pernille B Udesen

doi:10.3389/fmed.2019.00242

Abstract

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS.

Highlights

Polycystic ovary syndrome (PCOS) presents with a multifactorial etiology that includes genetic predisposition [1] and environmental factors
During January 2010–February 2013, we recruited 42 women diagnosed with PCOS according to the Rotterdam 2003 criteria and 20 healthy, age, and body mass index (BMI) matched, regular cycling women who were referred to the fertility clinic due to tubal factor infertility or male infertility
Both PCOS women and Controls were well matched for age and BMI (Table 1)

Summary

Introduction

Polycystic ovary syndrome (PCOS) presents with a multifactorial etiology that includes genetic predisposition [1] and environmental factors. Elevated androgen levels constitute a key feature in the pathogenesis of PCOS [5] with high testosterone (T) levels being linked with abdominal fat distribution [6], glucose intolerance [5], and insulin resistance [5] as well as ovulatory dysfunction [7]. Both androstenedione and T contribute to the total circulating androgen pool. Given that PCOS women already have an unfavorable metabolic profile in early adulthood, there is a need for PCOS patient stratification in terms of metabolic risk outcomes independently of the different PCOS phenotypes

Methods

Results

Conclusion