The Epigenetic Effects of Preconception Paternal Alcohol Exposure on Adult Health and Disease

Abstract

Alcohol is a notorious teratogen and a major driver of both mental and physical defects. Recently, alcohol has been discovered to exert intergenerational effects on offspring development. While maternal exposure to alcohol in-utero has been linked to the development of fetal alcohol spectrum disorders, paternal contributions to this disorder remain poorly understood. Emerging evidence suggest the association of paternal environmental exposures and long-term metabolic dysfunction1,2. Using a mouse model, our preliminary studies have identified an association between preconception paternal alcohol use and deficits in both the prenatal and postnatal growth of the offspring. These growth defects are accompanied by altered transcriptomic profiles in the fetal liver at gestation day (GD) 14.5, which persists into the adult stages. In this study, we will examine the mechanism by which paternal alcohol exposure drives the development of prenatal growth retardation and long-term postnatal growth restriction in the offspring, as well as the abnormal metabolic response of the offspring to dietary challenge.