Endocrine Abstracts

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition of unclear origin, characterized by hyperandrogenism (HA), oligo-/amenorrhoea (OM), and polycystic ovarian morphology (PCOM). According to the Rotterdam criteria, PCOS phenotypes A-D range from mild to severe and are defined as phenotype A (HA, OM and PCOM), phenotype B (HA, OM), phenotype C (HA, PCOM) and phenotype D (OM, PCOM). Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and may be potential biomarkers. Our main aim was to characterize miRNAs previously reported to be altered in PCOS, in women with different PCOS phenotypes.

Methods: We conducted a pilot study (n=51) with 11 women in each phenotype group and 8 control women. Candidate miRNAs were selected based on previously reported associations with PCOS. MiRNA isolation, complementary DNA (cDNA) synthesis and quantitative real-time PCR (qRT-PCR) were performed with assays from Qiagen. UniSp 2/4/5/6 were used as exogenous controls, and qRT-PCR data were normalized to the mean of miR-484 and snu6 as reference genes. After verifying the normal distribution and homogeneity of variances, a one-way-ANOVA or a non-parametric Kruskal-Wallis test was conducted, followed by Dunnet and Tukey’s post-hoc tests. The diagnostic value for discriminating a PCOS phenotype from the other phenotypes was calculated by area under the curve (AUC) and by a receiver-operating-characteristic (ROC) analysis. TargetScanHuman8.0 was used to identify potential target genes of differentially expressed miRNAs.

Results: Systemic expression of miR-23a-3p was upregulated in phenotype B and discriminated PCOS phenotype B from the other phenotypes (AUC=0.837; 95% confidence interval (CI), 0.706-0.968; P=0.006). MiR-424-5p was downregulated in phenotype C and discriminated this phenotype from the others (AUC=0.801; 95%CI, 0.591-1.000; P=0.007). A subgroup analysis between hyperandrogenic PCOS phenotypes (phenotypes A, B, C, n=32) and PCOS women without hyperandrogenism (phenotype D, n=8) showed no group specific differences in their miRNA expression profiles. Functional annotation of differentially expressed miRNAs revealed binding sites in genes of pathways related to insulin resistance and carbohydrate metabolism, iron and lipid metabolism, inflammation, steroid and peptide hormones as well as fertility.

Conclusion: Understanding the differential hormonal and miRNA profiles across various PCOS phenotypes is important to improve the pathophysiologic understanding of PCOS. The miRNAs identified, miR-23a-3p and miR-424-5p, hold promise as potential biomarkers for differentiating between specific PCOS phenotypes. These findings contribute to a deeper understanding of PCOS heterogeneity, potentially improving diagnostic and treatment strategies for women with PCOS.