{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:10:17Z","timestamp":1790079017362,"version":"4.0.1"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Accumulating evidence suggests that ferroptosis\u2014an iron\u2013dependent, lipid peroxidation\u2013driven form of regulated cell death\u2014may contribute substantially to ionizing radiation (IR)\u2013induced testicular injury. In this review, we develop a hypothesis\u2013generating framework for ferroptosis\u2013immune crosstalk in the testis. Within this framework, ferroptotic injury to Sertoli cells is proposed to compromise the blood\u2013testis barrier (BTB), potentially facilitating autoantigen exposure and adaptive immune activation; reciprocal inflammatory signaling may, in turn, increase the susceptibility of neighboring cells to ferroptosis. Potential interactions between ferroptosis and apoptosis, autophagy, pyroptosis, and necroptosis are considered as additional components of this proposed network. We summarize clinically used drugs and emerging strategies targeting ferroptosis, including iron chelators, radical scavengers, NRF2 activators, natural antioxidants, and nanomedicine. Key challenges such as the temporal dynamics of ferroptosis, dose\u2013dependent effects, and translational gaps are discussed. This framework is intended to organize current evidence, identify testable mechanistic links, and guide future studies of male fertility preservation through ferroptosis\u2013immune modulation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1935866","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:33:32Z","timestamp":1790076812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferroptosis\u2013immune crosstalk in ionizing radiation\u2013induced testicular injury: mechanisms and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Rong","family":"Xu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhao","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical 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