Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver

Abstract

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

Multi-omics Analysis of Aging Liver Reveals Changes in Endoplasmic Stress and Degradation Pathways in Female Nonhuman Primates

“…NHPs are ideal translational models because they share strikingly similar genetic, physiological, and behavior traits with humans (Tarantal et al 2022). Our recent NHP studies aim to better understand human disease processes have focused on genetics, epigenetics, caloric restriction, maternal caloric restriction and offspring health, maternal obesity and offspring health, NASH, and steatosis (Zimmerman et al 2023, Puppala et al 2022. In humans, studies comparing diseased vs. healthy liver have shown decline in cellular and biological functions (Wang et al 2023, Campagnoli et al 2022.…”