Alterations in sperm-inherited noncoding RNAs associate with late-term fetal growth restriction induced by preconception paternal alcohol use.

Using a mouse model, our group recently described an association between chronic paternal alcohol use prior to conception and deficits in offspring growth. Here, we sought to determine the impact of alcohol exposure on male reproductive physiology and the association of sperm-inherited noncoding RNAs with the transmission of the observed growth defects. Alcohol exposure did not appreciably alter male reproductive physiology or fertility. However, chronic alcohol use reproducibly induced late-term fetal growth restriction in the offspring, which correlated with a shift in the proportional ratio of transfer RNA-derived small RNAs to Piwi-interacting RNAs, as well as altered enrichment of microRNAs miR21, miR30, and miR142 in alcohol-exposed sperm. Although our dataset share similarities to prior works examining the impact of paternal stress on offspring phenotype, we were unable to identify any changes in plasma corticosterone, indicating alcohol may alter sperm-inherited noncoding RNAs through distinct mechanisms.