Perinatal exposure to low dose 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) alters sperm DNA methylation in adult rats.

Polybrominated diphenyl ethers (PBDEs) are a group of ubiquitous reproductive toxins. Given that spermatogenesis requires extensive epigenetic changes, we hypothesize that PBDEs impact sperm DNA methylation. Pregnant Wistar rats were exposed perinatally to 0.2mg/kg 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and caudal epididymal sperm were collected from offspring on postnatal days (PNDs) 65 and 120. Libraries were prepared from sperm DNA and sequenced with an average of 18.0 million unique reads per sample. Differential methylated regions (DMRs) were identified via MethPipe package. BDE-47 exposure increased DNA methylation of epididymal sperm on PND 65 in genes, promoters and intergenic regions; however, on PND120 methylation decreased in these genomic elements. We identified 21 and 9 exposure-related DMRs in sperm collected on PND65 and PND120, respectively. Two DMRs overlapped between the two time-points. This is the first study to demonstrate that environmentally-relevant perinatal exposure to PBDE results in long-lasting changes in sperm DNA methylation.