Embryology of esophageal atresia in the adriamycin rat model.
OBJECTIVE
The aim of this study was to describe the dysmorphogenetic process 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 their embryos recovered on days 12, 12.5, and 13 were serially sectioned in the transversal plane and studied microscopically after H&E and PAS staining. The findings were compared with those of age-matched untreated embryos.


RESULTS
All untreated and saline embryos were normal, whereas 49% of Adriamycin embryos had foregut malformations. Tracheoesophageal separation was complete on day 12 in control embryos, whereas 9 of 10 Adriamycin-exposed embryos had a common esophagotrachea with low emergence of the bronchi at that stage. This pattern had evolved into 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 of 13 embryos. Two had less well-defined malformations.


CONCLUSIONS
Esophagotrachea equivalent to complete tracheoesophageal cleft is the first step leading to EA + TEF in this model. The full-blown malformation is finally acquired by partial loss of the posterior wall of the foregut, which tapers-off in the mediastinal mesenchyme and respiratory differentiation of the anterior wall down to the level of bronchial bifurcation, where it constitutes the fistula and the distal esophagus.
Possögel
A K
AK
Department of Surgery, Hospital Infantil La Paz, Madrid, Spain.
Diez-Pardo
J A
JA
Morales
C
C
Navarro
C
C
Tovar
J A
JA
D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004933:Esophageal Atresia / Q000139:chemically induced / Q000196:embryology*; D005260:Female; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014138:Tracheoesophageal Fistula / Q000139:chemically induced / Q000196:embryology*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin