Effect of 900 MHz Electromagnetic Field Exposure During Different Trimesters of Pregnancy on TRPM2-Mediated Ferroptosis and Neurotoxicity in the Trigeminal Ganglion of Rats: Protective Role of Ferrostatin-1

Abstract

Electromagnetic field (EMF) exposure, unavoidable in modern life, is linked to oxidative stress and ferroptosis, processes linked to neurodevelopmental disorders. This study investigated the effects of EMF exposure during different pregnancy trimesters on rat offspring trigeminal ganglia (TGs), focusing on transient receptor potential melastatin 2 (TRPM2) ion channels, and assessed the neuroprotective potential of ferrostatin-1 (Fer), a ferroptosis inhibitor, against EMF-induced damage. Pregnant rats were exposed to 900 MHz EMF for 2 h/day during early (1-7 days, EMF 1), mid (8-14 days, EMF 2), or late (15-21 days, EMF 3) gestation. Fer (2.5 µmol/kg, i.p.) was administered immediately after daily EMF exposure in Fer treatment groups. Offspring TG tissues were analyzed on postnatal Day 28 using histopathological, immunohistochemical, and biochemical approaches. EMF exposure significantly reduced antioxidant capacity and elevated lipid peroxidation, reactive oxygen species (ROS), pro-inflammatory cytokines, apoptotic markers, and TRPM2 activation, with the most pronounced alterations in mid-gestation exposure. Fer administration largely normalized these parameters and reduced structural damage in TG. In conclusion, these findings suggest that prenatal EMF triggers ferroptotic/apoptotic neurodegeneration via TRPM2, and that Fer holds promise as a neuroprotective agent.