Ionizing radiation (IR) induced sex-specific reproductive and offspring developmental toxicity in Zebrafish

Ionizing radiation (IR) is a ubiquitous environmental radiation factor with natural and anthropogenic sources. The cumulative discharge of nuclear contaminated water into the ocean by Japan in the recent years has been making the impact of IR on aquatic living organisms a topic of great concern in both academic circles and public opinion. However, sex-specific mechanisms of IR-induced reproductive and offspring developmental toxicity remain poorly understood. Here, we investigated the sexually dimorphic effects of acute X-ray radiation on zebrafish (Danio rerio) reproduction using integrated phenotypic and molecular approaches. Transcriptome analysis revealed striking sexual dimorphism in radiation response, with male gonads showing extensive perturbation compared to female tissues. Female gonads exhibited coordinated protective responses characterized by enhanced immune system activation and membrane integrity maintenance, while male tissues showed significant disruption of iron homeostasis and oxidative stress pathways, particularly in ferroptosis-related genes. Paternal radiation induced more severe reproductive impairment compared to the maternal, as evidenced by reduced egg production and fertilization rates. Using transgenic zebrafish lines, we demonstrated that paternal predominantly drove developmental abnormalities in offspring, including vascular defects, increased immune cell infiltration, and neurological malformations. Radiation specifically damaged sperm morphology and motility. Compared to the ovaries, the testes suffered more severe oxidative damage and stress regulation issues, leading to more significant reproductive developmental disorders. Our findings provide molecular mechanistic evidence for sex-specific radiation sensitivity in aquatic organisms and highlight the importance of considering sexual dimorphism in radiation protection strategies.