Epigenetic transgenerational effects of prenatal exposure to 2,2′,4,4′-tetrabromodiphenyl ether on sperm function and DNA methylation in rat offspring

The global production and use of polybrominated diphenyl ethers, including 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), have been substantially curtailed in recent decades. However, BDE-47 remains ubiquitously detectable in environmental matrices and human tissues worldwide. In this study, we investigated whether prenatal exposure to BDE-47 disrupts sperm function and DNA methylation in rat offspring. Pregnant rats were treated with BDE-47 from gestational day 0 to parturition. Sperm count, motility, morphology, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, sperm chromatin DNA fragmentation index (DFI), serum testosterone, and histopathology were evaluated across generations. Testicular DNA methyltransferase expression and whole-genome bisulfite sequencing were performed to determine the DNA methylation in the F3 generation. BDE-47 exposure altered anogenital distance (AGD), sperm count, motility, morphology, MMP, ROS production, mean DFI, and %DFI in the F1 generation; AGD, morphology, and ROS production in the F2 generation; and AGD, motility, morphology, MMP, ROS production, mean DFI, %DFI, and testicular DNA methyltransferase expression in the F3 generation. Gene ontology analysis revealed that SYCP2, ASMT, and MSH4 were associated with sex differentiation and reproductive development. Our findings indicate that prenatal exposure to BDE-47 exerts transgenerational epigenetic effects, inducing phenotypic changes in the male reproductive system.