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

Abstract

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.

Maternal Nutrient Restriction Disrupts Gene Expression and Metabolites Associated with Urea Cycle, Steroid Synthesis, Glucose Homeostasis, and Glucuronidation in Fetal Calf Liver

“…In sheep, 30% maternal nutrient restriction for 15 days in mid-gestation suppressed gene expression regulating steroid and cholesterol synthesis, including HMGCS1 , in the fetal liver [ 20 ]. Meanwhile, global maternal nutrient restriction of 60% level in goats activated hepatic gene expression related to steroid biosynthesis and bile secretion, but not HMGCS1 [ 49 ], and increased metabolites related to bile acid metabolism, such as taurochenodeoxycholate and taurocholate [ 42 ]. Taken together with the suppression of FDPS , HSD11B1 , and HSD17B6 observed in this study, it is likely that MUN disturbs the gene expression and metabolism associated with steroid and bile acid synthesis in the fetal liver.…”

Prospect of potential intrauterine programming impacts associated with COVID-19

“…Additional studies in this field further pointed out that such long-term health consequences are associated with the nutritional status not only during fetal but also during the peri-conceptional or early postnatal period, leading to several conceptual frameworks, including the predictive adaptive responses ( 19 ), the developmental origin of health and diseases (DOHaD) ( 20 ). The hypotheses underlying these frameworks have been tested and confirmed in additional epidemiological studies, for example, using retrospective data from the Dutch famine (1944–1945) during the second world war ( 21 , 22 ), and also in several animal studies, including but not limited to sheep ( 23 – 25 ), goats ( 26 , 27 ), pigs ( 28 – 30 ), rodents ( 31 – 33 ), and monkeys ( 34 , 35 ). These studies suggest that during unfortunate circumstances for humanity (e.g., during wars, natural disasters, or global emergencies like pandemic COVID-19), women during the peri-conceptional period or pregnancy can be exposed to mild to severe forms of undernutrition.…”