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

Abstract

Overview

In recent years, growing evidence has highlighted significant concerns regarding the hazardous effects of radiofrequency electromagnetic radiation (RF-EMR) on male reproductive function. The search for viable protective agents to counteract these effects has brought attention to melatonin, known for its antioxidant and anti-apoptotic properties and its role in reproductive health. Yet, the molecular pathways through which melatonin shields against RF-EMR-induced reproductive damage have remained elusive.

Findings

• Prolonged exposure (8 weeks) to RF-EMR (2.45 GHz; power density 2.5 W/m²; SAR 0.125-0.5 W/kg) led to increased oxidative stress and ferroptosis in testicular tissue of male mice.
• The resulting oxidative damage from RF-EMR caused notable decreases in sperm quality.
• Administering melatonin notably reduced the testicular oxidative injury and inhibited ferroptosis induced by RF-EMR.
• Mechanistic studies demonstrated that melatonin counters reactive oxygen species (ROS) production and ferroptosis by activating the Nrf2 signaling pathway through MT1/MT2 receptors.

Conclusion

RF-EMR exposure is directly linked to harmful effects on male reproduction, primarily via ferroptosis in testicular tissue. Melatonin substantially protects against this RF-EMR-induced damage by activating the Nrf2 pathway, thereby suppressing ferroptosis. These results underscore the potential of melatonin as a therapeutic agent for male infertility linked to RF-EMR exposure. Further controlled trials are recommended to assess melatonin’s clinical benefit in addressing male reproductive damage caused by electromagnetic fields.