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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\u2010induced 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\u2010like 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\u2010induced PCOS rats showed increased levels of ER stress\u2010related genes and proteins. Hyperandrogen\u2010induced 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\u2010activated ER stress IRE1<jats:italic>\u03b1<\/jats:italic>\u2010XBP1 pathway. Dihydrotestosterone\u2010 (DHT\u2010) induced ER stress was mitigated by curcumin\/irisin or 4<jats:italic>\u03bc<\/jats:italic>8C (an ER stress inhibitor) in primary GC culture. In this in vitro model, the strongly expressed follicular development\u2010related genes <jats:italic>Ar<\/jats:italic>, <jats:italic>Cyp11\u03b11<\/jats:italic>, and <jats:italic>Cyp19\u03b11<\/jats:italic> were also downregulated.<\/jats:p>","DOI":"10.1155\/2021\/7382900","type":"journal-article","created":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T21:50:08Z","timestamp":1640555408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Curcumin in Combination with Aerobic Exercise Improves Follicular Dysfunction via Inhibition of the Hyperandrogen\u2010Induced IRE1<i>\u03b1<\/i>\/XBP1 Endoplasmic Reticulum Stress Pathway in PCOS\u2010Like 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