title: Intrauterine growth restriction alters postnatal colonic barrier maturation in rats.
abstract: Intrauterine growth restriction (IUGR) is a leading cause of perinatal mortality and morbidity and increases the risk for necrotizing enterocolitis. We hypothesized that colonic barrier disruption could be responsible for intestinal frailty in infants and adults born with IUGR. Mucins and trefoil factor family 3 (TFF3) actively contribute to epithelium protection and healing. Our aim was to determine whether IUGR affects colonic mucosa maturation. IUGR was induced by dietary protein restriction in pregnant dams. Mucins and Tff3 expression and morphologic maturation of the colonic mucosa were followed during postnatal development of the offspring. Before weaning, mucin 2 and Tff3 protein levels were reduced in colonic mucosa of rats with IUGR compared with controls. After weaning, expression of mucin 2 (mRNA and protein) and mucin 4 (mRNA) were lower in colonic mucosa of rats with IUGR. At the same time, IUGR was associated with a reduction of crypt depth and a higher percentage of crypts in fission. We conclude that IUGR impairs mucus barrier development and is associated with long-term alterations of mucin expression. The lack of an efficient colonic barrier induced by IUGR may predispose to colonic injury not only in neonatal life but also in later life.
authors.affiliation: UMR 1280, Physiologie des Adaptations Nutritionnelles, INRA, Université de Nantes, Nantes, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Fança-Berthon
authors.forename: Catherine
authors.initials: C
authors.lastname: Michel
authors.forename: Anthony
authors.initials: A
authors.lastname: Pagniez
authors.forename: Martine
authors.initials: M
authors.lastname: Rival
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Seuningen
authors.forename: Dominique
authors.initials: D
authors.lastname: Darmaun
authors.forename: Christine
authors.initials: C
authors.lastname: Hoebler
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000503:physiopathology; D004760:Enterocolitis / Q000209:etiology* / Q000503:physiopathology; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000503:physiopathology; D055262:Mucin-2 / Q000378:metabolism*; D055264:Mucin-4 / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011488:Protein Deficiency / Q000150:complications; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D000071165:Trefoil Factor-3
chemical_list: C524628:Muc2 protein, rat; C524660:Muc4 protein, rat; D055262:Mucin-2; D055264:Mucin-4; D009479:Neuropeptides; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3