Melatonin ameliorates RF-EMR-induced oxidative damage in mouse testis by inhibiting ferroptosis through Nrf2 pathway activation

Abstract Background In recent years, there has been increased examination of the harmful impacts of radiofrequency electromagnetic radiation (RF-EMR) on male reproductive ability, making it critical to explore effective protective measures. Melatonin has antioxidant and anti-apoptotic effects, and there is growing evidence that melatonin is beneficial to the reproductive process. The understanding of melatonin's biochemical mechanisms in safeguarding against testicular damage from RF-EMR exposure is limited. Results During the present investigation, it was observed that prolonged (8 weeks) exposure to RF-EMR [2.0 GHz; power density, 2.5 W/m 2 ; systemic specific absorption rate (SAR), 0.125-0.5 W/kg] may lead to decreased testosterone and melatonin concentrations in the serum, reduced sperm quality, increased apoptosis levels, and elevated oxidative stress in male mice. Notably, the administration of melatonin (at a dosage of 10 mg/kg via intraperitoneal injection) mitigated the oxidative harm to the testicles and ferroptosis caused by RF-EMR in mice. Mechanistically, melatonin may inhibit ROS production and ferroptosis by stimulating the Nrf2 signaling pathway through its receptors (MT1/MT2). Conclusion Taken together, these results indicate that melatonin could potentially improve oxidative harm caused by RF-EMR in the testes of mice by blocking ferroptosis through the activation of the Nrf2 pathway via MT1/MT2 receptors.