Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome.

Guannan Zhou,Jingxin Ding,Hongdao Zhang,Keqin Hua,Ganrong Zhang,Ligang Wu,Menglei Zhang,Yuanyuan Gu,Fangyue Zhou

doi:10.3389/fendo.2021.789939

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is a refractory reproductive disease and also a kind of endocrine and metabolic disease. Adipocyte cells can produce a mass of extracellular vesicles and orchestrate the status of other types cells. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS.MethodsThe crosstalk mediated by extracellular vesicle-miR-26b between adipocytes and CCs was determined in CC cells co-cultured with mature adipocytes or incubated with extracellular vesicle isolated from mature adipocytes. CCK-8 assay and flow cytometry were conducted in CCs treated with or without extracellular vesicles; microRNA (miRNA) sequencing was conducted for clarifying the key molecular. Hormone levels and ovary ovulation ability were conducted with animal experiment.ResultsThe results revealed that miR-26b was upregulated in extracellular vesicles derived from mature adipocytes. Adipocyte-derived extracellular vesicles inhibited viability and promoted apoptosis in CCs via targeting JAG1. Furthermore, extracellular vesicles derived from mature adipocyte disrupted the ovary ovulation and impaired the hormone levels.ConclusionsThese results identify a novel signaling pathway that adipocytes-derived extracellular vesicles-miR-26b promotes cell apoptosis in CCs and disrupted the ovary ovulation in the development of PCOS. The study indicates that adipose tissue-derived extracellular vesicles-miR-26b may play a key role in the PCOS and also provides insight into developing new therapeutic strategies for PCOS.

Highlights

Polycystic ovary syndrome (PCOS) is a common reproductive disorder among female individuals at reproductive age with an estimated incidence of 7%–9% [1]
To confirm the paracrine effect of mature adipocytes in inhibiting cumulus cells proliferation, CCs were co-cultured with mature adipocytes, pre-adipocytes, and DMEM medium in the Transwell system
These above results indicated that adipocytes inhibited CCs proliferation through secreted small molecules by stimulating cell apoptosis in vitro

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a common reproductive disorder among female individuals at reproductive age with an estimated incidence of 7%–9% [1]. As a kind of heterogeneous endocrine disorder, PCOS is reported to affect up to 20% reproductive-age women worldwide [2]. It is well acknowledged that PCOS is a complex disease involved in multisystem including reproductive, metabolic, and psychological features. It was reported that women with PCOS have an established increased risk of developing type 2 diabetes [5] and a still debated increased risk of cardiovascular disease [6]. Polycystic ovary syndrome (PCOS) is a refractory reproductive disease and a kind of endocrine and metabolic disease. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS

Objectives

Methods

Results

Discussion

Conclusion