Timing and embryology of esophageal atresia and tracheo-esophageal fistula.
The embryology of tracheo-esophageal anomalies is controversial. The development of an adriamycin-treated animal model has enabled improved understanding of the embryogenesis of these anomalies. Using this model, we aimed to describe the events leading to esophageal atresia and tracheo-esophageal fistula.



Timed-pregnant Sprague-Dawley rats were injected daily with adriamycin intraperitoneally at a dose of 2 mg/Kg on days 6-9 of gestation. Histological sections were prepared from 96 experimental and 34 control rat embryos at 11-14 days gestation (plug day = day 0).



The tracheal bud failed to develop normally from the foregut, leaving the foregut to give origin to both bronchi and differentiate into the respiratory system, and then continue as a fistula to the lower esophageal segment. Dorsal pouching of the proximal foregut, which is seen clearly on day 13, is responsible for the development of the upper esophageal segment.



We conclude that failure of the tracheal bud to develop normally from the primitive foregut is the main event which leads to the tracheo-esophageal anomalies. As the proximal part of the primitive foregut develops primarily into a trachea rather than an esophagus, the anomaly of the esophagus could be described as agenesis instead of atresia.
Merei
J M
JM
The F. Douglas Stephens Surgical Research Laboratory, Royal Children's Hospital, Melbourne, Australia.
Farmer
P
P
Hasthorpe
S
S
Qi
B Q
BQ
Beasley
S W
SW
Myers
N A
NA
Hutson
J M
JM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004933:Esophageal Atresia / Q000139:chemically induced / Q000196:embryology*; D004935:Esophageal Diseases / Q000139:chemically induced / Q000196:embryology*; D005260:Female; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014138:Tracheoesophageal Fistula / Q000139:chemically induced / Q000196:embryology*
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin