Mechanisms for the development of esophageal atresia☆☆☆

Abstract 

Background: There is no universally accepted theory to explain esophageal embryology and the abnormal development that produces esophageal atresia. Methods: The impact of Adriamycin administration on the pathogenesis of esophageal atresia was studied in the rat model of VATER association, from embryonic day (ED) 10 to ED 13. Results: Tissues in the ED10 Adriamycin-exposed embryos displayed less cell proliferation as shown by the reduced population of MIB-5-labelled cells. Cell apoptosis that is characteristic of the normal ED 12 lateral epithelial folds of the foregut (the prospective site of tracheoesophageal septation) was absent in the foregut of the Adriamycin-exposed embryo. Histologic examination of the ED 11-exposed embryo showed the presence of abnormal notochord that was stretched, split, or tethered to the foregut. This contrasts with the normal embryo in which the notochord was localized in close vicinity of the ventral part of the neural tube and separated from the foregut by ample amount of mesenchyme. The abnormal localization of the notochord was accompanied by the lack of down-regulation of the sonic hedgehog (Shh) activity in the prospective site of future tracheoesophageal separation in the exposed ED 12 embryo. Conclusion: The authors proposed that the ectopic location of the notochord leads to the disruption in Shh signalling that may underpin the development of esophageal atresia. J Pediatr Surg 36:985-994. Copyright © 2001 by W.B. Saunders Company.

Keywords:  Esophageal atresia, tracheoesophageal fistula, notochord, Sonic hedgehog, apoptosis, VATER, Adriamycin