P0989 - The Role of Maternal Stress-derived cortisol on Intestinal Development in Offspring

Background: Necrotizing enterocolitis (NEC) is characterized by damage to the intestinal tract, ranging from mucosal injury to full-thickness necrosis and perforation. Currently, it is unclear what triggers the development of NEC, but it is believed to have multifactorial causes, including intestinal immaturity and microbial dysbiosis. We hypothesize that heightened prenatal stress during pregnancy contributes to the development of NEC by interfering with intestinal development and microbial colonization in the offspring. Previous studies have shown that maternal stress during gestation impacts infant’s neurological development. However, little is known about how gestational stress affects intestinal development.

Methods: Using a Zebrafish model, we developed a methodology to induce chronic variable stress. The stressed fish were then mated and the offspring were analyzed compared to those derived from unstressed controls. To determine effects of stress on neurological development, we performed behavior analysis in the offspring. Using a TNBS-induced model of inflammation, we analyzed the gut by histology..

Results: We detected higher levels of cortisol in the stressed fish compared to controls. 6-day old larvae derived from stressed fish exhibited reduced thigmotaxis compared to unstressed larvae, indicative of anxiety like behavior. Similarly, in a novel tank test, stressed adults spent more time in the starting zone and less time exploring the novel tank compared to controls. These findings indicate parental stress negatively affects neurological development in the offspring. In the gut, following TNBS administration, stressed fish exhibited higher mortality and gut pathology compared to unstressed controls, likely due to inflammatory damage as a result of parental stress.

Conclusion: Prenatal stress modulates neurological and gastrointestinal development in the offspring. Further studies are underway to investigate the microbial dysbiosis and function of the gut in larvae derived from stressed fish.