Correlation between the follicular fluid extracellular-vesicle-derived microRNAs and signaling disturbance in the oocytes of women with polycystic ovary syndrome.

Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The quality of oocytes in PCOS patients remains poor, leading to poor pregnancy outcomes. The molecular mechanisms underlying the poor quality of oocytes in PCOS are not fully understood. This study aimed to explore the potential functional microRNAs (miRNAs) in follicular fluid (FF)-derived extracellular vesicles (FF-EVs) and their role in oocyte developmental competence in PCOS. We analyzed DEmiRNAs in FF-EVs and DEGs in oocytes from PCOS patients and controls using GEO database. We identified 14 potential functional DEmiRNAs in FF-EVs and predicted the target genes of 14 DEmiRNAs using TargetScan. We performed conjoint analyses between the target genes of these miRNAs and DEGs in oocytes, identifying 12 DEmiRNAs whose target genes overlap with oocyte DEGs. Thus, 12 functional DEmiRNAs were the hub miRNAs. These miRNAs were predicted to target genes involved in oocyte development and signaling pathways such as PI3K/Akt, Ras, and MAPK pathways. KEGG enrichment analysis suggested that these miRNAs might impair oocyte developmental competence in PCOS by dysregulating PI3K/Akt signaling pathway. qRT-PCR validated the increase of miR-93-3p and miR-152-3p, and the decrease of miR-625-5p and miR-17-5p in FF-EVs of PCOS patients. This study highlighted the significance of FF-EVs in the pathology of PCOS and revealed the potential role of the increase of miR-93-3p and miR-152-3p, and the decrease of miR-625-5p and miR-17-5p in impairing oocyte developmental competence in PCOS. Further research is needed to elucidate the specific mechanisms by which these miRNAs affect oocyte development and to explore the potential therapeutic implications.