Plasma exosomes and contained MiRNAs affect the reproductive phenotype in polycystic ovary syndrome

Anovulation is the main feature of infertile women with polycystic ovary syndrome (PCOS), and there is very limited understanding of the role of plasma exosomes and miRNAs in it. To identify the effect of PCOS patients' plasma exosomes and exosomal miRNAs, we isolated plasma exosomes of PCOS patients and normal women and injected into 8-week-old ICR female mice via tail vein. The changes in estrus cycle, serum hormone levels, and ovarian morphology were observed. KGN cells were cultured and transfected with mimics and inhibitors of differentially expressed exosomal miRNAs (miR-18a-3p, miR-20b-5p, miR-106a-5p, miR-126-3p, and miR-146a-5p) and then tested for steroid hormone synthesis, proliferation, and apoptosis. The results showed that female ICR mice injected with plasma exosomes from PCOS patients presented ovarian oligo-cyclicity. Hormone synthesis and proliferation of granulosa cells were affected by differentially expressed PCOS plasma-derived exosomal miRNAs, of which miR-126-3p having the most evident effect. MiR-126-3p affected the proliferation of granulosa cells by inhibiting PDGFR beta and its downstream PI3K-AKT pathway. Our results demonstrated plasma exosomes and contained miRNAs in PCOS patients affect the estrus cycle of mice, hormone secretion, and proliferation of granulosa cells. This study provides a novel understanding about the function of plasma exosomes and exosomal miRNAs in PCOS.