RNA-sequencing of liver samples derived from offspring sired by males chronically exposed to alcohol prior to conception

Using an established mouse model of chronic exposure, previous work by our group had linked preconception paternal alcohol use to sex-specific patterns of fetal growth restriction and placental dysfunction. The goal of the present study was to investigate the long-term impact chronic preconception paternal alcohol exposure has on offspring growth and metabolic programming. In the male offspring, we observed increases in both the expression of genes within the pro-fibrotic TGF-ß signaling pathway as well as total levels of cellular hydroxyproline within the liver. Further, we identified suppressed cytokine profiles, which could be linked to the up-regulation of genes in the LiverX/RetinoidX/FarnesoidX Receptor pathways. Postnatal day 90 male mice were provided access to either a solution of 10% (w⁄v) alcohol and 0.066% (w⁄v) Sweet ‘N Low (experimental) or 0.066% (w⁄v) Sweet ‘N Low alone (control) for four hours a day. Once consistent patterns of drinking were established, males were maintained on this protocol for a period of 70 days, which corresponds to the length of approximately two complete spermatogenic cycles. Once the 70-day milestone was surpassed, males were mated to unexposed dams and the offspring evaluated for growth.