Pathohistological study of adriamycin-induced tracheal agenesis in the fetal rat

There have been few studies of tracheal agenesis (TA) because it is an extremely rare condition and is invariably fatal. However, it is recognised to be associated with a variety of oesophageal abnormalities, including oesophageal atresia (OA) and communicating bronchopulmonary foregut malformations (CBPFM). Except for some gross pathological reports, there has been no detailed histological investigation of this congenital abnormality. Adriamycin-induced TA in fetal rats provides a means of studying this uncommon condition, including its relationship to oesophageal abnormalities. TA was induced in rat features by intraperitoneal injection of adriamycin (2 mg/kg) into timed-pregnant rats on days 6-9. Their 33 fetuses were removed by caesarean section, cut transversely, and stained after which the slides were examined. OA developed in 27/33 adriamycin-treated fetuses, TA occurred in 5. Four had type III while the 5th had type II TA. The oesophagus of fetuses with TA acquired tracheal features in the region where both ectopic bronchi originated. Two fetuses with TA also had OA, and 4 had a CBPFM. Other abnormalities detected involved the gastrointestinal, urinary and cardiovascular systems. The association of TA and oesophageal abnormalities suggests that there may be a spectrum of abnormalities comprising a number of variants, which may have a common aetiology. The other abnormalities co-existing in this animal model mirror those found in reported cases of human TA. Ultimately, the rat model of OA and TA may give insight into the embryogenesis of these malformations.