Metformin mitigates cisplatin-induced ovarian damage through inhibiting the pyroptosis of granulosa cells via ROS/TXNIP/NLRP3 signaling pathway

Cisplatin, a vital chemotherapy drug for solid malignant tumors, can detrimentally affect ovarian health and fertility in premenopausal patients with cancer. Currently, effective strategies to mitigate cisplatin-induced ovarian damage remain limited. Several studies have highlighted the potential of metformin as an anticancer agent with anti-aging properties and other health benefits. Hence, the present study established an animal model to investigate the impact of metformin on cisplatin-induced ovarian damage, elucidating its mechanisms using bulk RNA sequencing analysis and Western blotting. Our study findings demonstrate that metformin significantly prevents the decline in cisplatin-induced ovarian reserve, maintaining anti-müllerian hormone (AMH) and estradiol (E2) levels. Moreover, metformin may effectively improve cisplatin-induced ovarian fibrosis and granulosa cell pyroptosis through the ROS/TXNIP/NLRP3 pathway. In summary, our study indicates that metformin holds promise in alleviating cisplatin-induced ovarian damage, offering a potential avenue to preserve female fertility during chemotherapy.