Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring

FASEB J. 2019 Jan;33(1):770-781. doi: 10.1096/fj.201800079R. Epub 2018 Aug 1.


Early-life adversity is a major risk factor for the development of diseases later in life. Maternal protein restriction (MPR) is associated with morbidities in offspring affecting multiple organs, but its impact on the gastrointestinal (GI) tract remains poorly studied. Using a rat model, we examined the consequences of MPR on GI function and on the enteric nervous system (ENS) in the offspring at postnatal d 35 under basal state and following a water avoidance stress (WAS). Compared with control rats, MPR rats exhibited greater colonic motility, permeability, and corticosteronemia. In contrast to controls, MPR rats presented a blunted functional and corticosteronemic response to WAS. Furthermore, MPR rats showed an increased proportion of choline acetyltransferase-immunoreactive (ChAT-IR) neurons and a reduced level of autophagy in colonic myenteric neurons. In ENS cultures, corticosterone treatment increased the proportion of ChAT-IR neurons and reduced autophagy level in enteric neurons. Inhibition of autophagy in ENS cultures resulted in a higher vulnerability of enteric neurons to a cellular stress. Altogether, this study suggests that MPR induced GI dysfunction and ENS alterations in offspring rats and that MPR-induced increased corticosteronemia might be involved in ENS remodeling and altered responsiveness of the gut to stressors later in life.-Aubert, P., Oleynikova, E., Rizvi, H., Ndjim, M., Le Berre-Scoul, C., Grohard, P. A., Chevalier, J., Segain, J.-P., Le Drean, G., Neunlist, M., Boudin, H. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring.

Keywords: cortiscosterone; enteric neuron; nutritional programming; stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Body Size
  • Body Weight
  • Choline O-Acetyltransferase / metabolism
  • Colon / physiopathology
  • Corticosterone / blood
  • Dietary Proteins / administration & dosage*
  • Enteric Nervous System / enzymology
  • Enteric Nervous System / physiopathology*
  • Female
  • Gastrointestinal Tract / physiopathology*
  • Intestinal Absorption
  • Maternal Exposure*
  • Models, Animal
  • Neurons / enzymology
  • Neurons / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley


  • Dietary Proteins
  • Nitric Oxide Synthase Type I
  • Choline O-Acetyltransferase
  • Corticosterone