PSVI-2 - Multigenerational effects of maternal rate of body weight gain on fetal liver miRNA expression

Abstract: Maternal rate of gain is critical to heifer development, pregnancy outcomes, and cow longevity. Multigenerational epigenetic effects in offspring resulting from differing levels of maternal body weight gain in heifers have not been explored previously in beef cattle. The objective of this study was to evaluate the effects of early gestational body weight gain in beef heifers on epigenetic mechanisms regulating gene expression in the fetal liver of the F1 generation and to determine their persistence into the F2 generation. Therefore, we hypothesized that the heifer rate of body weight gain during early pregnancy would alter the hepatic micro-RNA (miRNA) expression profile of the F1 generation and that these effects would persist into the F2 offspring. Angus cross-bred heifers (n = 132; ~13 months of age) bred through artificial insemination were assigned to treatments targeting different rates of body weight gain (LG - Low gain targeting 0.28 kg/day, n = 66; or MG - Moderate gain targeting 0.79 kg/day, n = 66). Fifteen F0 pregnant heifers (LG=7, MG=8) were slaughtered on day 83 of gestation, and F1 fetal liver samples were collected. The remaining pregnant heifers (LG, n = 23; MG, n = 25) were maintained on pasture and managed as one group through calving and weaning, with no dietary treatments. The F1 heifers were then bred and slaughtered to collect the fetal liver tissues of the F2 generation from sixteen pregnant heifers (LG = 8, MG = 8) on day 83 of pregnancy. The fetal hepatic miRNA profiles of F1 and F2 generations were determined using miRNA-Seq. The data were analyzed using the mirDeep2 pipeline, and differentially expressed miRNAs were identified (FDR < 0.05). Bta-miR-206 was the only differentially expressed miRNA in both the F1 and F2 generations for the MG vs. LG comparison. Based on gene target predictions, 809 genes are targeted by this miRNA. Functionally over-represented pathways (FDR < 0.05) of targeted genes included key energy metabolic pathways like mTOR, Wnt, MAPK, and PI3K-Akt signaling pathways, along with thyroid hormone signaling and longevity-regulating pathways. The results indicated that the effects of the F0 maternal rate of gain persisted into the F1 and F2 generations, and the maternal rate of gain during early pregnancy altered the hepatic miRNA expression profile to potentially regulate energy metabolism in beef heifers.