How the Father Might Epigenetically Program the Risk for Developmental Origins of Health and Disease Effects in His Offspring

In addition to DNA, the sperm provides epigenetic factors to the embryo upon fertilization. DNA methylation, histone modifications, and small noncoding RNAs are critical for spermatogenesis and are present in mature sperm. Recent evidence suggests that a subset of these epigenetic modifications have roles beyond sperm function, providing transcriptional cues for early embryonic development. Numerous associations have been observed between paternal age, lifestyle, or chemical exposures and offspring health, with alterations seen in sperm epigenetic marks. These studies implicate epigenetic mechanisms in paternally inherited offspring phenotype. In this chapter, we outline the major epigenetic modifications established in sperm and explore possible modes of epigenetic inheritance from the sperm to the fertilized embryo. In addition, we provide evidence of environmental effects on the epigenetic state of paternal germ line and transmission of epigenetic alterations to offspring.