Maternal Nutrition during the First 50 Days of Gestation Alters Bovine Fetal Hepatic Metabolic Transcriptome

We hypothesized that maternal nutrition during the first 50 d of gestation would alter the metabolic transcriptome of the bovine fetal liver. Fourteen beef heifers were estrus synchronized and assigned to 2 treatments at breeding (CON, 100% of requirements to gain 0.45kg/d; RES, 60% of CON). Heifers were ovariohysterectomized on d 50 of gestation and fetal livers were dissected, flash frozen, RNA extracted, and RNA-Sequencing conducted. Transcriptome analysis was run via the Tuxedo Suite and KEGG Pathways were analyzed with DAVID 6.8. A total of 548 genes (P < 0.01) were used for pathway analysis, of which 201 were false discovery rate protected (q < 0.10). Fetal hepatic metabolic KEGG pathways resulted in 45 genes that were differentially expressed and grouped by function: amino acid metabolism (n = 10), purine and pyrimidine metabolism (n = 7), carbohydrate metabolism (n = 10), reducing equivalent (NAD/FAD) metabolism (n =5), steroid and lipid biosynthesis (n = 9), cytochrome and heme metabolism (n = 2), and 2 remaining unrelated genes. Five genes involved in amino acid metabolism were upregulated in CON vs. RES fetal liver (Min = 1.73; Max = 2.46; Avg = 1.99-fold). Five genes involved in amino acid metabolism were upregulated in RES vs. CON (Min = 1.63; Max = 2.36; Avg = 1.85-fold). Genes involved in purine and pyrimidine metabolism were upregulated in RES vs. CON (Min = 1.72; Max = 2.50; Avg = 1.94-fold). Five genes involved in carbohydrate metabolism were upregulated in CON vs. RES (Min = 1.61; Max = 3.50; Avg = 2.08-fold). Five genes involved in carbohydrate metabolism were upregulated in RES vs. CON (Min = 1.69; Max = 2.13; Avg = 1.92-fold). Genes involved in reducing equivalent metabolism were upregulated in RES vs. CON (Min = 1.63; Max = 1.92; Avg = 1.74-fold). Eight genes involved in steroid and lipid biosynthetic pathways were upregulated in RES vs. CON (Min = 1.61; Max = 2.07; Avg = 1.82-fold), and 1 gene was upregulated in CON vs. RES (1.70-fold). The two genes involved in cytochrome and heme metabolism were upregulated in RES vs. CON (Min = 2.53; Max = 3.18; Avg = 2.9-fold). These data are interpreted to support our hypothesis that a moderate maternal nutrient restriction during the first 50 d of gestation ‘programs’ the bovine fetal hepatic metabolic transcriptome primarily reflected by upregulation in RES offspring. USDA is an equal opportunity employer and provider.