Identification Of MicroRNAs In Human Follicular Fluid:Characterization Of MicroRNAs That Govern Steroidogenesis In Vitro And Are Associated With Polycystic Ovary Syndrome In Vivo

Human follicular fluid is a combination of proteins, metabolites, and ionic compounds that is indicative of the general state of follicular metabolism and is associated with maturation and quality of oocytes. Deviations in these components are often associated with reproductive diseases.miRNAs are small RNA molecules that modulate post-transcriptional gene regulation by binding to specific mRNA targets. We have identified microRNAs (abbr. miRNAs) in microvesicles and the supernatant of human follicular fluid. Bioinformatics analysis showed that the most highly expressed miRNAs targeted genes associated with reproductive, endocrine, and metabolic processes. In addition, we investigated whether any of the highly expressed miRNAs in the follicular fluid play roles in steroidogenesis. We found that miR-132, miR-320, miR-520c-3p, miR-24, and miR-222regulate estradiol concentrations and that miR-24, miR-193b, and miR-483-5p regulate progesterone concentrations. Finally, we showed that miR-132and miR-320are expressed at significantly lower levels in the follicular fluid of polycystic ovary patients than in healthy controls.These results substantially revise our understanding of the content of human follicular fluid and suggest novel pathophysiological links between miRNAs and polycystic ovary syndrome. This study lays the foundation for the future development of miRNAs as novel biomarkers for studying ovarian diseases and other pathophysiological processes.