Paternal alcohol exposures program intergenerational hormetic effects on offspring fetoplacental growth

• DOI: 10.3389/fcell.2022.930375
• Publication Date: 2022-08-11T12:12:54Z
• Authors: Kara N. Thomas; Katherine N. Zimmel; Alison Basel; Alexis N. Roach; Nicole A. Mehta; Kelly R. Thomas; Luke J. Dotson; Yudhishtar S. Bedi; Michael C. Golding
• Keywords: Hormesis; Toxicant; Maternal effect; Genomic Imprinting

Hormesis refers to graded adaptive responses harmful environmental stimuli where low-level toxicant exposures stimulate tissue growth and responsiveness while, in contrast, higher-level induce toxicity. Although the intergenerational inheritance of programmed hormetic is described plants insects, researchers have yet observe this phenomenon mammals. Using a physiologically relevant mouse model, we demonstrate that chronic preconception paternal alcohol program nonlinear, dose-dependent changes offspring fetoplacental growth. Our studies identify an inverse j-shaped curve with threshold 2.4 g/Kg per day; below threshold, ethanol increases placental growth, while doses exceeding point yield comparative decreases In male offspring, higher labyrinth layer but do not impact fetal hypertrophy induced by associate increased crown-rump length, particularly offspring. Finally, alterations physiology correlate disruptions both mitochondrial-encoded imprinted gene expression. Understanding influence on paternally-inherited epigenetic downstream may help explain enormous variation observed spectrum disorder (FASD) phenotypes incidence.