Transcriptome analysis reveals liver metabolism programming in kids from nutritional restricted goats during mid-gestation

BACKGROUND: Maternal nutrient restriction during pregnancy causes a metabolic disorder that threatens the offspring’s health in humans and animals. However, the molecular mechanism of how undernutrition affecting hepatic metabolism of fetal or postnatal offspring is still unclear. We aimed to investigate transcriptomic changes of fetal livers in response to maternal malnutrition in goats during mid-gestation and to explore whether these changes would disappear when the nutrition was recovered to normal level during mid-gestation using goats (Capra hircus) as the experimental animals. METHODS: Fifty-three pregnant goats were subjected to a control (100% of the maintenance requirements, CON) or a restricted (60% of the maintenance requirements on day 45 to day 100 of gestation and then realimentation, RES) diet. A total of 16 liver samples were collected from fetal goats on day 100 of gestation and goat kids of postnatal day 90 to obtain hepatic transcriptional profiles using RNA-Seq. RESULTS: Principal component analysis of the hepatic transcriptomes presented a clear separation by growth phase (fetus and kid) rather than treatment. Maternal undernutrition up-regulated 86 genes and down-regulated 76 genes in the fetal liver of the FR group as compared to the FC group. KEGG pathway analysis showed the DEGs mainly enriched in protein digestion and absorption, steroid biosynthesis, carbohydrate digestion and absorption and bile secretion. A total of 118 significant DEGs (fold change > 1.2 and FDR < 0.1) within KR vs. KC comparison was identified with 79 up-regulated genes and down-regulated 39 genes, and these DEGs mainly enriched in the biosynthesis of amino acids, citrate cycle, valine, leucine and isoleucine biosynthesis and carbon metabolism. CONCLUSION: Hepatic transcriptome analysis showed that maternal undernutrition promoted protein digestion and absorption in the fetal livers, while which restrained carbohydrate metabolism and citric acid cycle in the livers of kid goats after realimentation. The results indicate that maternal undernutrition during mid-gestation causes hepatic metabolism programming in kid goats on a molecular level.