Abstract

Endometriosis (EMs) is a common cause of ovarian dysfunction and infertility, closely linked to iron overload-induced oxidative stress and ferroptosis. While electroacupuncture (EA) has shown promise in treating reproductive disorders, its role in regulating ovarian ferroptosis in EMs remains unclear. This study aimed to investigate the protective effects and underlying mechanisms of EA on ovarian function in a mouse model of EMs, which simulated the chronic pelvic hemorrhage observed in patients. Comprehensive evaluations were performed using hematoxylin-eosin staining, qRT-PCR, Western blot, immunohistochemistry, immunofluorescence, and biochemical assays to assess ovarian function, iron metabolism, oxidative stress, and ferroptosis-related markers. The results demonstrated that EA treatment significantly restored estrous cyclicity, increased ovarian weight and index, improved serum hormone levels, promoted multi-stage follicular development, and reduced follicular atresia. EA also alleviated ovarian iron overload and oxidative stress. Mechanistically, EA activated the Nrf2 pathway and its downstream targets, upregulated the anti-ferroptotic protein GPX4, suppressed the pro-ferroptotic factor ACSL4, and consequently reduced lipid peroxidation. In conclusion, this study reveals that EA mitigates granulosa cell ferroptosis and ameliorates EMs-induced ovarian injury by activating Nrf2 to enhance GPX4 activity and inhibit ACSL4-mediated lipid peroxidation. These findings provide experimental evidence supporting EA as a potential complementary therapy for EMs-related infertility.