Neural crest-derived defects in experimental esophageal atresia

Esophageal atresia (EA) is often associated with cardiovascular and other m alformations that are likely neural crest derived. The present study tests the hypothesis that the heart and great vessels and the thymus and parathyr oids may be abnormal in the rat model of EA as a result of disturbed neural crest development. Time-mated pregnant rats received intraperitoneally on d 8 and 9 of gestation either 2 mg/kg adriamycin or vehicle. Esophageal, he art, and thymic malformations were sought under the microscope in term fetu ses. The parathyroids were histologically investigated. Control fetuses had no malformations, whereas 69 of 109 fetuses exposed to adriamycin had EA a nd 45 of 69 had 15 right aortic arches, nine aberrant right subclavia, eigh t ventricular septal defects, six narrow pulmonary outflow tracts, five tet ralogies of Fallot, three double outflow right ventricles, three double aor tic arches, three atrial septal defects, three right ductus arteriosus, and two truncus. The thymus was absent in 19, hypoplastic in 12, and ectopic i n five out of 36 fetuses with EA in which it was studied, whereas the parat hyroid glands were absent in 16, single in four, and ectopic in one of the 23 fetuses with EA in which they were studied. In conclusion, the nature of the cardiovascular, thymic, and parathyroid malformations associated with EA in rats is consistent with the hypothesis of neural crest participation in their pathogenesis. Mechanisms simultaneously disturbing foregut septati on, somitic segmentation, and neural crest development should be sought to explain the combined occurrence of malformations in EA.