Melatonin ameliorates RF-EMR-induced reproductive damage by inhibiting ferroptosis through Nrf2 pathway activation

In recent years, there has been increased attention to the deleterious impacts of radiofrequency electromagnetic radiation (RF-EMR) on male reproductive ability, necessitating the exploration of effective protective measures. Melatonin has antioxidant and anti-apoptotic effects, and there is growing evidence of its benefit to the reproductive process. However, the biochemical mechanisms by which melatonin protects against reproductive damage from RF-EMR exposure are unknown. Here, we found that prolonged (8 weeks) exposure to RF-EMR [2.45 GHz; power density, 2.5 W/m²; whole-body specific absorption rate (SAR), 0.125-0.5 W/kg] induced ferroptosis and oxidative stress in testicular tissue, leading to a decrease of sperm quality in male mice. Notably, the administration of melatonin mitigated the oxidative harm to the testicles and ferroptosis caused by RF-EMR in mice. Mechanistically, melatonin could inhibit ROS production and ferroptosis by stimulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway through its receptors (MT1/MT2). Taken together, these results indicate that melatonin could potentially improve RF-EMR-induced reproductive damage in male mice by blocking ferroptosis through activation of the Nrf2 pathway.