Ionizing radiation impairs ovarian function by inducing DNA double-strand breaks, oxidative stress, and inflammatory cascades, leading to primordial follicle depletion and premature ovarian insufficiency (POI). Core mechanisms involve ATM/p53-mediated DNA damage response, granulosa cell apoptosis triggered by a sharp increase in reactive oxygen species/reactive nitrogen species (ROS/RNS), and Toll-like receptor (TLR)/NF-κB-driven chronic inflammation. Currently, only amifostine and palifermin are internationally approved radioprotective agents, yet they exhibit significant limitations including severe toxicity, narrow indications, and lack of conclusive evidence for ovarian protection. Investigational agents like the natural antioxidant melatonin require further clinical validation for ovarian radioprotection. Emerging strategies, such as TLR5 agonists, mitochondrial-targeted agents, and targeted drug delivery systems, provide novel directions for mitigating radiation-induced ovarian injury. This review synthesizes key pathways of radiation-induced ovarian damage, explores cutting-edge mechanisms, and highlights promising novel radioprotective agents. The proposed synergistic “epigenetic regulation + immunomodulation” strategy embodies a paradigm shift from passive mitigation to active precision protection against ovarian radiation damage.

The survival rate of cancer patients was improved due to the development of cancer treatment techniques, and thus the fertility protection for young female cancer patients has attracted increasing attention. Radiotherapy, as one of the comprehensive cancer treatment, could cause ovarian damage in adolescent and child-bearing women, which leads to fertility decline and a series of side effects. Radiation can cause ovarian damage not only by acting on biological macromolecules directly, but also by increasing oxidative stress between oocytes and ovarian granulosa cells indirectly. At present, the fertility preservation of female cancer patients undergoing radiotherapy mainly includes physical protection, drug protection and biological protection. Recently, the development of new technologies for the preservation of fertility in female cancer patients has also brought new hope, including factors such as protective effects, patient age, and the selection of specific cancer treatment measures, which are the main considerations in the selection process of fertility preservation measures. This article reviews the research progress on radiation-induced ovarian damage, with a focus on the introduction of the fertility preservation measures and new technologies for young female tumor patients receiving radiotherapy.