title: Prenatal intestinal obstruction affects the myenteric plexus and causes functional bowel impairment in fetal rat experimental model of intestinal atresia.
abstract: BACKGROUND
  Intestinal atresia is a rare congenital disorder with an incidence of 3/10,000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders.
  
  
  RESULTS
  We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression.
  
  
  CONCLUSIONS
  Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care.
authors.affiliation: INSERM U989, Paris, France. naziha.khen-dunlop@nck.aphp.fr
authors.forename: Naziha
authors.initials: N
authors.lastname: Khen-Dunlop
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.forename: Anais
authors.initials: A
authors.lastname: Victor
authors.forename: Celine
authors.initials: C
authors.lastname: Grosos
authors.forename: Sandrine
authors.initials: S
authors.lastname: Menard
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Soret
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goudin
authors.forename: Maud
authors.initials: M
authors.lastname: Pousset
authors.forename: Frederique
authors.initials: F
authors.lastname: Sauvat
authors.forename: Yann
authors.initials: Y
authors.lastname: Revillon
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001285:Atropine; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005315:Fetal Diseases / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D006735:Horseradish Peroxidase; D006801:Humans; D007231:Infant, Newborn; D007409:Intestinal Atresia / Q000503:physiopathology*; D008353:Mannitol; D009197:Myenteric Plexus / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000166:cytology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010539:Permeability; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D008353:Mannitol; D001285:Atropine; D006735:Horseradish Peroxidase; D019001:Nitric Oxide Synthase; D002795:Choline O-Acetyltransferase; D019331:NG-Nitroarginine Methyl Ester