The Effects of Gestational Psychological Stress on Neonatal Mouse Intestinal Development

Background: Psychological stress during pregnancy has been shown to cause subsequent harm to the fetus and newborn. Many studies focus on neurodevelopmental outcomes, but little is known about the effect of gestational stress on intestinal immunity and development. The purpose of this study was to determine the effect of psychological stress during pregnancy on intestinal architecture and growth in newborns. Methods: Eight-week-old C57BL6 littermates underwent timed breeding. Pregnant dams were subjected to 1 h of daily psychological stress by using a well-established restraint model during days E7-E14. The distal ileum of 2-wk-old offspring of stressed mothers and nonstressed controls was harvested for histologic analysis. Slides were blinded to measure villus height and crypt depth and surface area. Serum was obtained to measure serum corticosterone levels. An explant model was used to measure corticosterone on the intestinal stem cell marker Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) and growth factors epidermal growth factor receptor and insulin-like growth factor-1. Results: The villus height, crypt depth, and surface area were significantly decreased in newborn exposed to stress during gestation. In addition, corticosterone levels were elevated in 2-wk-old mice exposed to stress. Real-time polymerase chain reaction revealed that explants exposed to corticosterone had a decrease in LGR5 compared with controls and an increase in epidermal growth factor receptor. Conclusions: Here, we establish that neonatal mice from mothers that were subjected to psychological stress during pregnancy have significantly shorter villi and crypts compared with controls. In addition, pups from stressed mothers have decreased expression levels of the intestinal stem cell marker LGR5. These findings will aid in determining the effect of gestational psychological stress on intestinal development and stem cell plasticity.