The Regulation of ZAR1 on Apoptosis and Mitophagy in Ovarian Granular Cells and Primary Ovarian Insufficiency (POI) Mice.

Abstract

Primary ovarian insufficiency (POI) has become a serious problem causing infertility and endocrine disorders in women of child-bearing age. There is an urgent demand for novel drugs or targets to address the apoptosis, autophagy and mitochondria damage associated with ovarian aging. This study focused on the regulation of zygote arrest 1 (ZAR1) in ovarian function and its potential role in POI. We collected clinical samples, established POI cell and mouse models using 4-vinylcyclohexene diepoxide (VCD), and investigated the effects of ZAR1 in KGN cells and POI mice. We found that ZAR1 expression was negatively associated with follicle-stimulating hormone (FSH) in POI women. ZAR1 overexpression inhibited apoptosis activation, cell cycle arrest and mitophagy, but the protection effects can be blocked by autophagy inhibitor. Mice with lower expression of ZAR1 exhibited more severe ovarian damages. These findings indicated that ZAR1 is a novel target for prevention and treatment of ovarian aging.