Notochord-gut failure of detachment and intestinal atresia

Abstract

A spectrum of congenital anomalies have been described in an adriamycin-treated model with common features to the human pattern. Multiple intestinal atresias was part of this spectrum occurring in 25% of full-term experimental rat fetuses. The aim of this study was to examine the underlying developmental mechanism that results in intestinal atresia. Virgin timed-pregnant Sprague-Dawley rats were injected with Adriamycin i.p. at a dose of 2 mg/kg on days 6-9 of gestation. Embryos were removed on different gestational days during organogenesis and serial transverse histologic sections were examined and compared with control specimens. In experimental embryos, hindgut atresia was seen in day 12 embryos. Attachment of the intestine with the notochord was obvious observation resulting in abnormal position of the intestine. In some specimens the atretic intestine was splitting the dorsal aorta or even located behind the dorsal aorta. It is concluded that in the adriamycin-animal model, notochord-intestinal failure of detachment resulted in intestinal atresia during the beginning of organogenesis period. The possible underlying mechanisms are pinching of some endodermal cells as well as interference with normal intestinal circulation resulting in ischemic necrosis.