Abstract

Simple SummaryHyperandrogenemia (HA) is the main pathophysiological change that takes place in polycystic ovary syndrome (PCOS). Cyproterone acetate (CYA) is a drug commonly used to reduce androgen in patients with PCOS. Long-term and continuous exposure to hyperandrogen can cause ovarian granulosa cells (GCs), pyroptotic death, and follicular dysfunction in PCOS mice. The aim of this study was to investigate whether CYA could ameliorate HA-induced pyroptosis of PCOS ovarian GCs by alleviating the activation of the IRE1α signaling pathway. The results of this study showed that HA induced the pyroptosis of ovarian GCs by activating the IRE1α signaling pathway in mouse ovarian granulosa cells and KGN cells. CYA can alleviate the occurrence of ovarian GC pyroptosis by inhibiting the activation of the IRE1α signaling pathway. This study provides a new mechanism and evidential support for CYA in the treatment of PCOS patients.AbstractObjective: Hyperandrogenemia (HA) is the main pathophysiological change that takes place in polycystic ovary syndrome (PCOS). Cyproterone acetate (CYA) is a drug commonly used to reduce androgen in patients with PCOS. Long-term and continuous exposure to HA can cause ovarian granulosa cells (GCs), pyroptotic death, and follicular dysfunction in PCOS mice. The aim of this study was to investigate whether CYA could ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs by alleviating the activation of the IRE1α signaling pathway. Methods: Firstly, thirty PCOS patients with HA as their main clinical manifestation were selected as the study group, and thirty non-PCOS patients were selected as the control group. The GCs and follicular fluid of the patients were collected, and the expression of pyroptosis-related proteins was detected. Secondly, a PCOS mouse model induced by dehydroepiandrosterone (DHEA) was constructed, and the tre