Ameliorating effects of rTMS on spermatogenesis disorder caused by cranial radiation-induced abscopal effects

The study investigated the potential ameliorating effects of repetitive transcranial magnetic stimulation (rTMS) on spermatogenesis disorder caused by cranial radiation-induced abscopal effects (RIAEs). Male C57BL/6 mice were randomized into Sham, Sham+rTMS, Rad and Rad+rTMS groups. Cranial irradiation (5 Gy/day at 2.33 Gy/min for 4 consecutive days) was administered to Rad groups, followed by rTMS (10 Hz, 1.2 T, figure-8 coil, 1000 pulses/day, 5 days/week for 4 weeks) in rTMS intervention groups. Evaluations included sperm parameters, testicular morphology, Sertoli cell function, and spermatogonial stem cells (SSCs) dynamics. Mechanistic analyses focused on inflammatory markers, oxidative stress indicators, and hypothalamic-pituitary-gonadal (HPG) axis hormones. rTMS significantly improved spermatogenic-related endpoints in irradiated mice, evidenced by increased sperm count with reduced abnormalities, preserved testicular architecture and SSCs activity, attenuated oxidative damage, balanced cytokine profiles and normalized neuroendocrine regulation. These findings suggest that rTMS may potentially mitigate spermatogenesis disorder caused by cranial RIAEs through multimodal mechanisms involving oxidative stress mitigation, inflammatory homeostasis restoration, and neuroendocrine axis regulation. This study provides preclinical evidence for rTMS as a potential non-invasive candidate strategy for mitigating spermatogenic impairment during cranial radiotherapy, with further validation required to confirm its utility for fertility preservation. • Central-peripheral modulation rTMS eases radiotherapy-induced sperm damage via tissue redox regulation, systemic anti-inflammation, HPG axis repair. • Selective fertility protection : Improves sperm quality, preserves testicular structure and BTB integrity, and rescues SSCs proliferation via dual SCF regulation. • Translational potential rTMS offers a safe fertility preservation strategy for neurocranial radiotherapy patients.