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

Area of Science:

• Neonatal immunology
• Developmental biology
• Gastroenterology

Background:

• Immature neonatal immune systems can dysregulate inflammatory signaling, contributing to pediatric diseases like necrotizing enterocolitis (NEC).
• NEC pathogenesis is multifactorial, with microbial dysbiosis and intestinal immaturity implicated as triggers.
• Prenatal stress is a potential, yet understudied, contributor to NEC development.

Purpose of the Study:

• To investigate the hypothesis that psychological stress during pregnancy negatively impacts offspring intestinal development.
• To identify gene expression changes in offspring gut tissue following maternal prenatal stress.
• To explore the role of specific stress-induced genes in intestinal inflammation and NEC pathogenesis.

Main Methods:

• RNA sequencing (RNASeq) analysis of offspring small intestine following maternal chronic stress during gestation.
• Identification of differentially expressed genes (DEGs) and biological pathways.
• Assessment of C3 upregulation and its contribution to tissue injury in a mesenteric ischemia model.

Main Results:

• Prenatal stress led to significant gene expression alterations in the offspring gut.
• The complement component 3 (C3) gene was notably upregulated in the small intestine of offspring exposed to prenatal stress.
• Upregulated C3 expression correlated with increased tissue injury scores in a model of intestinal ischemia.

Conclusions:

• Prenatal psychological stress adversely affects offspring intestinal development and gene expression.
• Upregulated C3 in the neonatal gut may be a key mediator of stress-induced intestinal inflammation and injury.
• These findings suggest a novel pathway linking maternal stress to pediatric intestinal diseases like NEC.