Identification of exosomal miRNAs specifically derived from intrafollicular cells in women with polycystic ovary syndrome

Abstract Research Question To identify the exosomal miRNAs specifically derived from intrafollicular cells in women with polycystic ovary syndrome polycystic ovarian syndrome (PCOS) and investigate their biology functions. Design A total of 120 females were recruited in this study from September 2017 to October 2018. To investigate miRNAs profiles in exosomes derived from follicular fluid and serum, 30 PCOS patients and 30 non-PCOS patients were included for miRNAs microarray which contain probes interrogating 2549 human miRNAs. To study the expression levels of differentially expressed miRNAs, exosomes in follicular fluid obtained from another 30 PCOS patients and 30 non-PCOS patients were used for qRT-PCR analysis. Results A total of 281 exosomal miRNAs specifically derived from intrafollicular cells were identified, among which 179 miRNAs expressed in both PCOS and non-PCOS group. 26 out of 179 intra-follicle-specific exosomal miRNAs were predicted to target 1537 genes. Functional analysis suggested that these genes were involved in pathways related to folliculogenesis including MAPK, TNF-β, and PI3K-Akt signaling pathway. qRT-PCR analysis showed that the expression of seven intra-follicle-specific exosomal miRNAs was significantly higher in follicular fluid-derived exosomes in PCOS females than that in non-PCOS females. We identified that these miRNAs and their corresponding target genes involved in MAPK signaling pathway and oocyte meiosis. Conclusion(s) Our data suggest that the aberrantly expressed miRNAs and their targeted genes might be associated with PCOS, providing novel insights for the molecular mechanisms of the regulation of folliculogenesis and oocyte maturation in PCOS.