EMBRYOLOGY OF ESOPHAGEAL ATRESIA IN THE ADRIAMYCIN RAT MODEL

Purpose: The aim of this study was to describe the dysmorphogenetic pr ocess leading to esophageal atresia and tracheoesophageal fistula (EA + TEF) in the recently developed Adriamycin model of the malformation. Methods: Time-mated pregnant rats were given either Adriamycin (1.75 mg/kg intraperitoneally) or saline on days 6 to 9 of gestation, and th eir embryos recovered on days 12, 12.5, and 13 were serially sectioned in the transversal plane and studied microscopically after H&E and PA S staining. The findings were compared with those of age-matched untre ated embryos. Results: All untreated and saline embryos were normal, w hereas 49% of Adriamycin embryos had foregut malformations. Tracheoeso phageal separation was complete on day 12 in control embryos, whereas 9 of 10 Adriamycin-exposed embryos had a common esophagotrachea with l ow emergence of the bronchi at that stage. This pattern had evolved in to that of a regular EA + TEF in all nine malformed embryos by day 13. On day 12.5, esophagotrachea was found in 6 of 13 and EA + TEF in 5 o f 13 embryos. Two had less weft-defined malformations. Conclusions: Es ophagotrachea equivalent to complete tracheoesophageal cleft is the fi rst step leading to EA + TEF in this model. The full-blown malformatio n is finally acquired by partial loss of the posterior wall of the for egut, which tapers-off in the mediastinal mesenchyme and respiratory d ifferentiation of the anterior wall down to the level of bronchial bif urcation, where it constitutes the fistula and the distal esophagus. C opyright (C) 1998 by W.B. Saunders Company.