Chronic paternal Wi-Fi RF-EMR exposure impairs placental efficiency and fetal growth: Association with sex-dependent histone modification patterns in mice.

The widespread use of Wi-Fi-derived radiofrequency electromagnetic radiation (RF-EMR) has raised concerns regarding male reproductive health; however, whether paternal exposure exerts transgenerational effects on offspring development remains unclear. This study investigated the effects of chronic paternal 2.4 GHz Wi-Fi RF-EMR exposure (whole-body SAR 0.125-0.5 W/kg, 4 h/day, 6 days/week for 20 weeks) on sperm quality in F0 male mice and placental development in F1 offspring, with a focus on epigenetic regulation. Paternal RF-EMR exposure significantly reduced sperm concentration and increased the sperm abnormality rate in F0 males. F1 offspring exhibited reduced fetal weight and placental efficiency, with more pronounced impairments in male offspring. Mechanistically, paternal exposure reduced the proportion of placental labyrinth layer and downregulated multiple nutrient transporters in a male-biased manner. Epigenetic analysis revealed sex-dependent histone modifications in placentas following paternal RF-EMR exposure: male placentas exhibited increased H3K9me2/3, H3K27me3, H3K27ac, and H3K4me2, whereas female placentas exhibited decreased H3K4me2. ChIP-qPCR targeting transporter promoters revealed sex-specific enrichment of repressive histone marks in placentas from exposed fathers. In male placentas, H3K27me3 was increased at the Atp1a1 and Slc22a3 promoters, and H3K9me3 was increased at the Atp1a1 and Slc2a1 promoters. In female placentas, H3K27me3 at the Slc3a2 promoter was significantly decreased. Collectively, chronic paternal Wi-Fi RF-EMR exposure impairs fetal growth and placental efficiency, with male offspring being more susceptible, and is associated with disrupted placental structure, impaired nutrient transport, and sex-dependent histone modifications in the offspring placenta. These findings underscore the importance of considering paternal RF-EMR exposure in reproductive risk assessment.