BFGF Mitigates CTX-Induced Ovarian Cytotoxicity via SERPINE1/HIF-1 and Nrf-2/HO-1 Signaling Pathways

Chemotherapy-induced ovarian damage is a significant concern for female cancer patients, often resulting in infertility, hormonal imbalance, and premature ovarian failure. Cyclophosphamide (CTX), a widely used chemotherapeutic agent, is highly effective against tumors but causes severe ovarian cytotoxicity. This study explores the protective effects of basic fibroblast growth factor (BFGF) and its underlying mechanisms in mitigating CTX-induced ovarian damage. BFGF treatment significantly enhanced cell viability, reduced apoptosis, and restored mitochondrial membrane potential in CTX-treated ovarian cells. Transcriptomic analysis revealed that BFGF activated the SERPINE1/HIF-1 signaling pathway, promoting angiogenesis, reducing apoptotic signaling, and enhancing cell cycle progression by upregulating Cyclin D1 and CDK4. Additionally, BFGF activated the Nrf-2/HO-1 pathway, boosting cellular defenses against oxidative stress and mitigating mitochondrial dysfunction. Functional studies confirmed that the inhibition of SERPINE1 or BFGF abrogated these protective effects, underscoring the critical roles of these pathways. These findings demonstrate that BFGF protects ovarian cells from CTX-induced damage by modulating the SERPINE1/HIF-1 and Nrf-2/HO-1 pathways, reducing apoptosis, and enhancing cell survival, providing a promising foundation for developing BFGF-based therapies to preserve ovarian function and fertility in female cancer patients undergoing chemotherapy.