139 Downregulation of mitochondrial metabolism is a driver for fetal adaptation to maternal nutrient restriction during gestation in beef cattle.

Abstract Nutritional stress in livestock refers to the inadequate or disproportionate intake of nutrients required for metabolic processes, normal physiological function, and growth. Unfortunately, inadequate nutrition in livestock is a common occurrence for producers, particularly in cow-calf operations. Therefore, understanding how maternal nutritional stressors affect offspring’s growth and development is crucial to the cow-calf segment of the beef supply chain. The objective of this study was to identify the cellular pathways affected by maternal nutrient restriction in beef cattle during gestation. A total of 36 fetuses were examined: 18 fetuses from dams that were given either a restricted (RES) or an adequate (ADQ) diet from day 160 to 240 of gestation. At day 240 of gestation, dams underwent Cesarean section for fetal removal, morphometrics, blood and tissue collection. Liver tissue samples were sequenced via Illumina platforms and analyzed by DESeq2, while the screening threshold was set at |log2(FoldChange)| >= 1 and Padj < = 0.05. Enrichment analysis of the differential expressed genes (DEGs) was performed by annotating genes to biological processes (Gene Ontology terms) and metabolic pathways (KEGG pathways). Genes with an adjusted P-value ≤ 0.05 were assigned as differentially expressed. A total of 2,327 genes were identified as differentially regulated between the groups. Of these 1,106 genes were up-regulated and 1,221 are down-regulated in RES vs. ADQ fetuses. KEGG pathway enrichment analysis showed that four mitochondrial metabolic pathways had significant downregulation of genes in RES vs. ADQ fetuses. These pathways include: Oxidative phosphorylation with a total of 53 genes and 52 were down regulated (Padj < 5.07-10). Thermogenesis with a total of 69 genes and 59 were down regulated (Padj < 8.08-9). Non- alcoholic fatty liver disease (NAFLD) with a total of 42 genes and 40 were downregulated (Padj < 5.18-6). Ribosome with a total of 76 genes and 76 were down regulated (Padj < 6.68-9). Thus, by utilizing omics approaches we found that fetal adaptations to maternal nutrient restrictions are connected to mitochondria, exhibiting a downregulation in mitochondrial metabolic processes. Funded by NIFA CBG # 2021-38821-34599.