PSVII-13 - Influence of early maternal gestational weight gain on liver gene expression across generations in offspring

Abstract: Maternal nutrition in the periconceptional period influences gene regulation in the fetal liver across generations, affecting long-term metabolism. This study aimed to examine the effects of the dams’ rate of body weight gain (F0) during early gestation on the differential gene expression of the liver of first (F1) and second-generation (F2) offspring. Crossbred Angus heifers (F0) were assigned into two groups based on their targeted rate of weight gain during the first 84 days of gestation: low gain (LG; 0.28 kg/day; n=8) or moderate gain (MG; 0.79 kg/day; n=8). Following this period, all heifers (F0) were kept on a forage-based diet until the F1 offspring were weaned at eight months. The F1 heifers underwent estrus synchronization and were artificially inseminated at 15 months of age. Liver samples were obtained from the F1 heifers at birth and later when harvested at 84 days of gestation, along with liver samples from their F2 fetuses, for a comprehensive multigenerational RNA-Seq analysis. Differentially expressed genes (DEGs) were identified using the DESeq2 R-package, focusing on significant genes determined by a p-value ≤0.05 and a log2 fold change |0.5|. Metabolic pathways and biological processes were analyzed using the WebGestalt tool to understand the implications of the observed gene expression changes. At birth, F1 heifers from MG dams exhibited 281 DEGs, comprising 152 downregulated and 129 upregulated genes compared to the offspring of LG dams. These genes were over-represented in lipid metabolism, cellular homeostasis, and signaling pathways such as MAPK and chemokine signaling. At harvest, 159 DEGs were identified in F1 heifers, with 67 genes downregulated and 92 genes upregulated in the MG group. These genes were related to cellular morphogenesis and biogenesis processes, with a notable downregulation of metabolic pathways. For the F2 fetuses, 192 DEGs were identified, where 71 genes were downregulated, and 121 genes were upregulated. These genes were involved in biological functions such as peptide secretion to cell proliferation and signaling pathways, including PI3K-Akt and Hippo signaling. The analysis of DEGs shared between F1 heifers and F2 fetuses highlighted the influence of the F0 dams' moderate weight gain. At birth and harvest, F1 heifers shared three genes (NAV2, FAM131C, SH3D21). F1 heifers at birth and F2 fetuses shared five genes (CD3E, H1-12, SLC7A11, PIP4P2, ENSBTAG00000051730). From the harvest at day 84 in F1 heifers and F2 fetuses, five genes were shared (DCDC2, RIN1, ENSBTAG00000008911, ENSBTAG00000040518, ENSBTAG00000048049). No DEGs were shared across all comparisons. These findings emphasize the multigenerational impact of dams’ early gestational weight gain on liver gene expression, influencing metabolic pathways and signaling across generations.