Anti-polycystic ovary syndrome effect of electroacupuncture: IMD inhibits ER stress-mediated apoptosis and autophagy in granulosa cells

Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy “acupuncture”. However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro. EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD1-53 suppressed cell apoptosis, autophagy and PERK/eIF2α/ATF4/CHOP signaling in T-induced KGN cells. Consistent with IMD1-53, ER stress inhibitor 4-PBA exerted an inhibitory effect on T-induced cell apoptosis and autophagy in KGN cells. Collectively, this study validates the protective effect of EA on DHEA-induced PCOS, and proposes that IMD relieved apoptosis and autophagy in T-induced granulosa cells via inhibiting ER stress.