MON-234 Targeted Profiling of Plasma MicroRNAs in Women with Polycystic Ovary Syndrome (PCOS): Impact of Obesity

BACKGROUND. Polycystic ovary syndrome (PCOS) is a common though heterogeneous endocrine and metabolic disorder in women of reproductive age. PCOS is characterized by polycystic ovaries, hyperandrogenism and chronic anovulation, as well as being associated with infertility, chronic low-grade inflammation, insulin resistance and increased risk of type 2 diabetes. MicroRNAs (miRNAs) are small, non-coding RNA molecules which regulate gene expression at the post-transcriptional level, and seen as candidate biomarkers for several conditions, including PCOS. HYPOTHESIS. Insofar as altered miRNA levels were associated with inflammation, diabetes, and insulin resistance, circulating miRNAs present in whole blood, serum, and plasma of women with PCOS patients were described as potential biomarkers for PCOSdiagnosis.The aim of this study was to characterize circulating miRNA profiles in women with PCOS compared to healthy women, and in cases and control women sub-grouped according to obesity status. METHODOLOGY. miRNA expression profile was assessed in the plasma of 12 women with PCOS (6 obese and 6 non-obese), compared to 12 age-and ethnically-matched eumenorrheic control women. Circulating miRNA was extracted from maternal plasma, and the differential expression of 84 miRNA species were determined using customized pathway-focused miRNA profiler kits. MAJOR RESULTS. The expression of 16 miRNAs (let-7d-5p, miR-17-5p, miR-181c-5p, miR-125a-5p, miR-301a-3p, miR-373-3p, miR-381-3p, miR-20b-5p, miR-144-3p, miR-15b-5p, miR-511, miR-520e, miR-875-3p, miR-130a-3p, miR-9-5p, and miR-98-5p)was different between women with PCOS and female controls. Obesity interacted with the differences in several of these miRNAs. Among obese subjects, differential expression of let-7d-5p, miR-125a-5p, miR-20b-5p, miR-144-3p, miR-15b-5p, miR-511, miR-520e, miR-875-3p, miR-130a-3p, miR-9-5p, and miR-98-5p was noted between PCOS cases and controls. By comparison, the expression of let-7d-5p, miR-17-5p, miR-181c-5p, miR-125a-5p, miR-301a-3p, miR-373-3p, miR-381-3p, miR-144-3p, miR-511, miR-130a-3p were different between women with PCOS and control women. Further analysis identified let-7b-5p (P = 0.028) and let-7d-5p (P = 0.036) were over-expressed, while miR-511 (P= 0.024) was under-expressed in PCOS cases. In addition, let-7c (P = 0.045), miR-34c (P = 0.034), and miR-524 let-7b-5p (P = 0.029) were under-represented in PCOS cases than in control subjects. CONCLUSIONS.The association of (low grade) chronic inflammatory state with PCOS is evident in the substantial altered miRNA expression in women with PCOS. Our results confirm the contribution of miRNA to PCOS pathogenesis, which may be predictive of specific PCOS phenotypes. Further studies are necessary to validate the miRNA diagnostic and prognostic utility.