Department of Surgery, Birmingham, AL, United States.
Department of Genetics, Birmingham, AL, United States.
Immunobiology. 2020 Jul;225(4):151983. doi: 10.1016/j.imbio.2020.151983. Epub 2020 Jul 6.
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.
未成熟新生儿免疫系统炎症信号的失调激活可能导致许多儿科疾病的发生，包括坏死性小肠结肠炎（NEC）。虽然发病机制尚不清楚，但NEC 被认为具有多种病因。微生物失调和肠道不成熟被认为是这种疾病的潜在触发因素。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，并导致 NEC 的发生。与这一假设一致，我们之前观察到，在怀孕期间长期处于应激状态的小鼠所生的幼崽的小肠绒毛变短，总表面积减少。在这项研究中，我们对怀孕小鼠产前应激后代肠道的基因表达变化进行了 RNA-seq 分析，并鉴定出了几个差异表达基因（DEGs）和生物学途径。值得注意的是，与未受应激的对照组相比，C3 在小肠中上调，并导致肠系膜缺血模型中的组织损伤评分更高。我们讨论了这些应激诱导的基因表达变化及其对肠道炎症发展的潜在影响。
