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. 2026 Sep 22;17:1935866. doi: 10.3389/fimmu.2026.1935866

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Copyright © 2026 Xu, He, Feng, Cai, Zhao, Xin, Zhang, Qin and Wang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Infographic illustrates six steps in radiation-induced testicular injury: Iron/Fenton axis, lipid peroxidation, antioxidant defense restoration, ferritinophagy/iron release, ferroptosis-immune amplification, and blood-testis barrier repair, including potential intervention points for each step. — Potential intervention targets within the proposed ferroptosis-immune crosstalk framework. Candidate therapeutic strategies are mapped to distinct pathological nodes of IR-induced testicular injury. Upstream interventions target labile iron accumulation and Fenton chemistry, lipid peroxidation, NCOA4-mediated ferritinophagy, mitochondrial oxidative stress, and impaired SLC7A11-GSH-GPX4/FSP1 antioxidant defenses. Downstream strategies target DAMP-associated HMGB1-RAGE/TLR4 signaling, pro-inflammatory macrophage activation, inflammatory cytokine amplification, and disruption of the blood-testis barrier. Tissue-repair and delivery approaches, including MSC-derived exosomes and targeted nanomedicine, may provide additional strategies for restoring the spermatogenic microenvironment. The diagram summarizes candidate intervention points and does not imply that these approaches have been clinically validated for radiation-induced testicular injury. Some graphical elements were created with BioRender.com.