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Background: Hyperandrogenism is a common characteristic of polycystic ovary syndrome (PCOS). Long-term, continuous exposure to hyperandrogenic environments may cause excessive endoplasmic reticulum (ER) stress in ovarian granulosa cells (GCs). Curcumin is a polyphenol extracted from turmeric rhizomes which has several pharmacological effects that may benefit patients with PCOS. To explore whether curcumin can inhibit hyperandrogen-induced ER stress in ovarian GCs of PCOS rats and to elucidate the possible underlying mechanisms., Methods: We developed PCOS model rats by exposure to hyperandrogenic conditions and divided the rats into control, PCOS, and PCOS+curcumin (200 mg/kg, for 8 weeks) groups. The levels of ER stress-related proteins and PI3K/AKT phosphorylation were measured in the ovarian tissue of all experimental groups by real-time quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence. Subsequent in vitro analysis on primary cultured GCs was performed to confirm the influence of curcumin on ER stress inhibition by immunofluorescence and western blotting., Results: Curcumin protects GCs from hyperandrogen-induced apoptosis in PCOS model rats by inhibiting the ER stress-related IRE1 α -XBP1 pathway and activating the PI3K/AKT signaling pathway., Conclusions: These observations indicate that curcumin might be a safe and useful supplement for PCOS patients., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Yaling Zhang et al.)

Combining diet with exercise can improve health and performance. Exercise can reduce androgen excess and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients. Curcumin is also presumed to improve the follicle development disorder. Here, we investigated the effects of a combination therapy of oral intake of curcumin and exercise on hyperandrogen-induced endoplasmic reticulum (ER) stress and ovarian granulosa cell (GC) apoptosis in rats with PCOS. We generated a PCOS model via continuous dehydroepiandrosterone subcutaneous injection into the necks of Sprague Dawley rats for 35 days. PCOS-like rats then received curcumin treatment combined with aerobic (treadmill) exercise for 8 weeks. We found that compared to control rats, the ovarian tissue and ovarian GCs of hyperandrogen-induced PCOS rats showed increased levels of ER stress-related genes and proteins. Hyperandrogen-induced ovarian GC apoptosis, which was mediated by excessive ER stress and unfolded protein response (UPR) activation, could cause follicle development disorders. Both curcumin gavage and aerobic exercise improved ovarian function via inhibiting the hyperandrogen-activated ER stress IRE1 α -XBP1 pathway. Dihydrotestosterone- (DHT-) induced ER stress was mitigated by curcumin/irisin or 4 μ 8C (an ER stress inhibitor) in primary GC culture. In this in vitro model, the strongly expressed follicular development-related genes Ar , Cyp11α1 , and Cyp19α1 were also downregulated., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Yaling Zhang et al.)