A father’s legacy: the sperm epigenome, preimplantation development, and paternal environment

Abstract

Paternal exposure to the environment can influence offspring phenotypes via a process known as intergenerational epigenetic inheritance. Such form of inheritance involves the sperm epigenome that is subjected to modifications by paternal exposure, which are carried from the father to the next generation. After fertilization, paternally inherited changes can manifest in the embryo and result in modified phenotypes later in life. To be long-lasting, these changes must either persist, escape the epigenetic reprogramming occurring after fertilization or be reinstated by guiding mechanisms during early development. This review discusses how the sperm epigenome instructs transcription and early embryonic development, and how environmental exposure can reshape this epigenetic information to influence developmental and transcriptional programs in the embryo. It addresses the patterns of penetrance in intergenerational epigenetic inheritance and considers how the sperm and embryonic epigenome can contribute to the variability of inherited phenotypes.