Connection between granulosa cell pyroptosis and oocyte endoplasmic reticulum stress in a mouse model of polycystic ovary syndrome.

INTRODUCTION: Low oocyte maturation rate was a common clinical manifestation in patients with polycystic ovary syndrome. Whether ovarian granulosa pyroptosis ultimately leads to low oocyte maturation rate through endoplasmic reticulum stress in oocytes is currently lacking in relevant research. MATERIALS AND METHODS: A PCOS model was established by treating mice with dehydroepiandrosterone (DHEA), and a CPA + PCOS ameliorator model was established by treating mice with the androgen antagonist cyproterone acetate (CPA) combined with DHEA. The levels of pyroptosis and endoplasmic reticulum (ER) stress-related proteins were measured. In addition, an culture system in vitro oocyte was established. After inhibiting pyroptosis of granulosa cells with CPA and the pyroptosis inhibitor disulfiram (DMF), the levels of ER stress-related proteins in oocytes and the oocyte maturation rate were determined. RESULTS: Compared with the control group, the expression levels of pyroptosis-related proteins such as GSDMD and Caspase-1 in granulosa cells and ER stress-related proteins such as p-IRE1α and p-PERK in oocytes were significantly increased in the PCOS group induced by high androgen levels, while the oocyte maturation rate was significantly decreased. After treatment with CPA and DMF, the expression levels of pyroptosis-related proteins in ovarian granulosa cells and ER stress-related proteins in oocytes were significantly lower than those in the PCOS group, while the oocyte maturation rate was significantly higher than those in the DHT group. In an in vitro oocyte co-culture system, the expression levels of pyroptosis-related proteins in granulosa cells and ER stress-related proteins in oocytes were significantly upregulated in the DHT group compared with the control group. After treatment with CPA and DMF, the expression levels of pyroptosis-related proteins in granulosa cells and ER stress-related proteins in oocytes were significantly lower than in the DHT group. CONCLUSION: High androgen induced pyroptosis of ovarian granulosa cells in a mouse model of PCOS, leading to ER stress in oocytes and a decrease of the oocyte maturation rate. Effective alleviation of granulosa cell pyroptosis can inhibit ER stress in oocytes and improve their maturation rate. This study provides new therapeutic targets for improving oocyte maturation in PCOS.