Characterization of altered microRNAs related to different phenotypes of polycystic ovarian syndrome (PCOS) in serum, follicular fluid, and cumulus cells

Abstract

Objective: Polycystic ovarian syndrome (PCOS) is a metabolic syndrome in which steroidogenesis, folliculogenesis, and cellular adhesion play crucial roles in its prognosis. These pathways are controlled and regulated by some small non-coding RNAs called microRNAs (miRs). Several miRs have differential expression in PCOS compared to healthy women, and their dysregulation suggests important roles of miRs in PCOS pathophysiology. However, the role of miRs is still unclear, especially in various phenotypes of PCOS.

Materials and methods: This study was conducted to evaluate the diagnostic potential of miR-212-3p, miR-490-5p, miR-647, and miR-4643 in different subtypes of PCOS. Accordingly, nineteen PCOS patients with different subtypes based on Rotterdam criteria (A: 8, B: not detected in this study, C: 5, and D: 6 patients) and six control age and BMI matched women under ICSI treatment were selected. The relative expression of miRs was then measured in blood serum before hormonal treatment (S1) and before ovum pickup (S2), follicular fluid (FF), and cumulus cells (CC) in all subjects. Also, the expression of miRs predicted target genes (AMH, AR, CYP11A1, CYP17A1, CYP19A1, GDF9, and HSD17B12) were done in the CC of understudy groups.

Results: In general, the results indicated that PCOS significantly increased the expression of miR-212-3p, miR-490-5p, and miR-4643 in FF and CCs compared to control. Although these miRs tend to increase in serum 1 of the PCOS patients, the differences were insignificant. However, there was a significant reduction in the expression of miR-647 in FF and CCs between PCOS vs. control. In addition, the miRs had significantly different expressions in various phenotypes of PCOS. For example, high levels of miR-647 in S2 and low levels of miR-490 in FF and miR-212 in CC can differentiate phenotype A from the other. Also, upregulation of miR-212 in FF and miR-4643 in S1 and low levels of this miR in FF can specifically differentiate subtype A from D. On the other hand, high levels of miR-4643 in FF and miR-490 in CC and lower titter of miR-647 can distinguish subtype C from the other. On the other hand, high levels of AMH, AR, CYP11, CYP17, and HSD17 in the hyperandrogenic PCOS and upregulation of CYP19A1 in the hypoandrogenic group can validate the role of selected miRs in the prognosis of PCOS.

Conclusion: Characterization of altered microRNAs in serum, FF, and CCs and their targets in CC showed that the miRs might play critical roles in steroidogenesis and folliculogenesis. These miRs may be used for molecular classification of PCOS subtypes and as biomarkers for PCOS diagnosis.

Keywords: Biomarker; Phenotype; Polycystic ovarian syndrome; microRNA.