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 < 0.01) 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 = 0.001) 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.

Communications Biology
Department of Biology

Beal, M.A. (Marc A.), Meier, M.J. (Matthew J.), Williams, A. (Andrew), Rowan-Carroll, A. (Andrea), Gagné, R. (Rémi), Lindsay, S.J. (Sarah J.), … Yauk, C.L. (2019). Paternal exposure to benzo(a)pyrene induces genome-wide mutations in mouse offspring. Communications Biology, 2(1). doi:10.1038/s42003-019-0476-5