Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring

Abstract

Understanding the effects of environmental exposures on germline mutation rates has been a decades-long pursuit in genetics. We used next-generation sequencing and comparative genomic hybridization arrays to investigate genome-wide mutations in the offspring of male mice exposed to benzo(a)pyrene (BaP), a common environmental pollutant. We demonstrate that offspring developing from sperm exposed during the mitotic or post-mitotic phases of spermatogenesis have significantly more de novo single nucleotide variants (1.8-fold; P\u2009<\u20090.01) than controls. Both phases of spermatogenesis are susceptible to the induction of heritable mutations, although mutations arising from post-fertilization events are more common after post-mitotic exposure. In addition, the mutation spectra in sperm and offspring of BaP-exposed males are consistent. Finally, we report a significant increase in transmitted copy number duplications (P\u2009=\u20090.001) in BaP-exposed sires. Our study demonstrates that germ cell mutagen exposures induce genome-wide mutations in the offspring that may be associated with adverse health outcomes.Marc Beal et al. investigate the genomic consequences of paternal exposure to benzo(a)pyrene (BaP), a common carcinogenic pollutant found in car exhaust fumes, tobacco smoke and grilled meats. They find that mouse offspring from males exposed to BaP have more de novo mutations, suggesting BaP exposure in males is associated with adverse health outcomes in offspring.