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.

未成熟的新生儿免疫系统对炎症信号的失调激活可能导致许多儿科疾病的发展，包括坏死性小肠结肠炎 (NEC)。虽然发病机制尚不清楚，但据信 NEC 有多种原因。微生物失调和肠道不成熟被认为是这种疾病的潜在诱因。我们假设怀孕期间的心理压力会对后代肠道组织的发育产生负面影响，并有助于 NEC 的发育。与这一假设一致，我们之前观察到来自妊娠期间长期压力的小鼠的幼崽的绒毛更短，小肠总表面积减少。在这项研究中，我们进行了 RNASeq 分析，以确定怀孕小鼠产前应激后后代肠道中的基因表达变化，并确定了几个差异表达基因 (DEG) 和生物学途径。值得注意的是，与无压力对照相比，C3 在小肠中被上调，并有助于肠系膜缺血模型中更高的组织损伤评分。我们讨论了这些压力诱导的基因表达变化的潜在影响及其对肠道炎症发展的贡献。