Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS)

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous reproductive disease. Adipose mesenchymal stem cells (AMSCs) can produce a mass of exosomes. The objective of this study was to determine the effects of exosomal miR-323-3p on cumulus cells (CCs) of PCOS patients. Exosomal miR-323-3p were collected from modified AMSCs. Real-time PCR, western blots, MTT assays, flow cytometry, luciferase reporter assays and a letrozole-induced PCOS mouse model were used to identify mechanisms of exosomal miR-323-3p on CCs. The results revealed that miR-323-3p expression was upregulated in AMSCs, exosomes and CCs. Upregulated miR-323-3p promoted cell proliferation and suppressed apoptosis in CCs, while miR-323-3p inhibitor exerted opposite roles in exosome-treated CCs. Moreover, PDCD4 was upregulated in PCOS CCs, displayed an inverse expression pattern to those of miR-323-3p, and was a direct target of miR-323-3p. Overexpression of PDCD4 reversed the effects of upregulated miR-323-3p on CCs. Serum FSH, LH and testosterone were upregulated while E2 levels were downregulated in the PCOS mice. Upregulation of miR-323-3p alleviated PCOS by suppressing CCs’ apoptosis through targeting PDCD4 in vivo. The results demonstrated that exosomal miR-323-3p promoted cell proliferation and inhibited apoptosis in CCs through targeting PDCD4 in PCOS. This study provides insight into developing new therapeutic strategies for PCOS.