Evidence of a common pathogenesis for foregut duplications and esophageal atresia with tracheo-esophageal fistula

The pathogenesis of the alimentary tract duplications, including foregut du plications (FgD) remains speculative. The accidental finding of FgD in feta l rats with esophageal atresia and tracheoesophageal fistula (EA-TEF) induc ed by Adriamycin provided an animal model to investigate a possible relatio nship between these two entities. Timed-pregnant rats were intraperitoneall y injected with Adriamycin (1.75 mg/kg) on gestational Days 6 to 9. Their e mbryos were harvested by Caesarean section from gestational Days 14 to 21. Forty-six of embryos were processed and serially sectioned in the transvers e or sagittal planes. EA-TEF occurred in 43/46 (93%) embryos of which 11 (2 4%) were found to have an associated FgD located at the level where the eso phagus was absent. Six FgDs communicated with the foregut or the trachea. F ive noncommunicating FgDs were located between the foregut and the vertebra l column. In the control embryo, the notochord was located in the centre of the vertebral column from Day 11 of the gestation. In Day 14, 15 and 16, h owever, embryos exposed to Adriamycin, an abnormal notochord or branch freq uently was located within the mesenchyme of the maldeveloped foregut or att ached to the duplication cyst. In some, it appeared that the notochord was drawing the cyst-like structure away from the foregut. The present study co nfirms that duplications adjacent to the esophagus arise from the foregut a nd that failure of the foregut to detach from the notochord at the normal t ime may contribute to the development of foregut duplications. Anat Rec 264 :93-100, 2001. (C) 2001 Wiley-Liss, Inc.