RNASeq analysis reveals upregulation of complement C3 in the offspring gut following prenatal stress in mice.

Dysregulated activation of inflammatory signaling by the immature neonatal immune system could lead to the development of many pediatric diseases including necrotizing enterocolitis (NEC). While the mechanism(s) of pathogenesis is unknown, NEC is believed to have multifactorial causes. Microbial dysbiosis and intestinal immaturity have been implicated as potential triggers for this disease. We hypothesized that psychological stress during pregnancy negatively impacts the development of intestinal tissues in offspring and contributes to development of NEC. Consistent with this hypothesis, we previously observed shorter villi and a decrease in total surface area in the small intestine of pups derived from mice that were chronically stressed during gestation. In this study, we performed RNASeq analysis to determine the gene expression changes in the offspring gut following prenatal stress in pregnant mice and identified several differentially expressed genes (DEGs) and biological pathways. Notably, C3 was upregulated in the small intestine and contributed to a higher tissue injury score in a mesenteric ischemia model compared to unstressed controls. We discuss the potential implications of these stress-induced genes expression changes and their contribution to development of intestinal inflammation.