DNA methylation and other epigenetic modifications mediating the transgenerational impacts of paternal exposures on offspring phenotypes

For many decades, it was assumed that germ cells delivered genetic information from both parents at conception, but that environmental exposures did not begin to modulate offspring phenotypes until postconception, including in utero and postnatal stages. Recent evidence, particularly from the past decade, from a range of species (including mice, rats, and humans) has demonstrated that paternal environmental exposures and experience prior to conception can epigenetically modulate male germ cells and lead to changes in offspring phenotypes. These epigenetic changes, in their broadest definition, not only include DNA chromatin modifications but also noncoding RNAs. Furthermore, differential paternal environmental exposures and experience can lead to sexually dimorphic changes in offspring phenotypes, largely through unknown mechanisms. These discoveries have forced us to reconsider Lamarckian evolution and consider whether accumulating evidence for epigenetic inheritance should lead to a new synthesis of Darwinian and Lamarckian evolutionary processes. Here, we will focus specifically on epigenetic mechanisms involving DNA modifications, and methylation in particular, with respect to paternal germ cells and the modulation of offspring phenotypes.