Intergenerational effects of maternal rate of body weight gain on the multi-omics hepatic profiles of bovine fetuses

Maternal periconceptual nutrition affects the growth trajectory of developing fetuses by modulating gene expression. The regulatory mechanisms and their role in fetal development remain underexplored in livestock models. Herein, we investigated the effects of maternal rate of body weight (BW) gain during early gestation on the DNA methylation, microRNA profiles, and their interaction with the hepatic gene expression in female fetuses. At breeding, 36 crossbred beef heifers (∼13 months of age) were randomly assigned to a nutritional plane to gain Low (0.28 kg/day; LG, n = 18) or Moderate (0.79 kg/day; MG, n = 18) BW through the first 83 days of gestation. A subset of pregnant heifers (n = 17) was selected, and fetal liver samples were collected on day 83 of gestation for DNA methylation and miRNA-Sequencing. After data quality control, miRDeep2 and Bismark tools were used to analyze miRNA and methylation data, respectively. The bta-miR-206 was the only differentially expressed miRNA (FDR = 0.02). Eight differentially methylated genes were identified (DMGs, FDR < 0.1). The over-represented pathways and biological processes (adj. p < 0.05) for bta-miR-206 targeted genes were associated with embryonic development, energy metabolism, and mineral transport, whereas the DMGs regulated anatomical structural development and transcriptional regulation. Our results show that key genes involved with liver metabolism, tissue structure, and function were regulated by DNA methylation and the miR-206. However, further investigation is warranted to determine physiological responses and long-term consequences on animal performance.