Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model.

Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated β-galactosidase activity.

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry.

Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry.