title: Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis.
abstract: BACKGROUND
  The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model.
  
  
  METHODS
  Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used.
  
  
  RESULTS
  In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls.
  
  
  CONCLUSIONS
  Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.
authors.affiliation: Department of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krebs
authors.forename: Michael
authors.initials: M
authors.lastname: Boettcher
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schäfer
authors.forename: Georg
authors.initials: G
authors.lastname: Eschenburg
authors.forename: Katharina
authors.initials: K
authors.lastname: Wenke
authors.forename: Birgit
authors.initials: B
authors.lastname: Appl
authors.forename: Beate
authors.initials: B
authors.lastname: Roth
authors.forename: Thomas
authors.initials: T
authors.lastname: Andreas
authors.forename: Carla
authors.initials: C
authors.lastname: Schmitz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fahje
authors.forename: Birthe
authors.initials: B
authors.lastname: Jacobsen
authors.forename: Bastian
authors.initials: B
authors.lastname: Tiemann
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinshagen
authors.forename: Kurt
authors.initials: K
authors.lastname: Hecher
authors.forename: Robert
authors.initials: R
authors.lastname: Bergholz
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D005332:Fetoscopy; D020139:Gastroschisis / Q000473:pathology / Q000601:surgery*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D056885:Interstitial Cells of Cajal / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology; D011247:Pregnancy; D012756:Sheep