Notochord involvement in experimental esophageal atresia

Esophageal atresia (EA) is often accompanied by vertebral defects and other anomalies. The adriamycin rat model of EA has disclosed the embryology of the malformation and shown that the vertebrae and notochord are also abnorm al. This study describes the nature of notochord malformations in rat embry os exposed to adriamycin. Time-mated rats received either 1.75 mg/kg adriam ycin or vehicle i.p. on gestational days (E) 6 to 9; E-12, E-12.5, and E-13 embryos were harvested, embedded in paraffin, and serially sectioned at 3 mu m in transverse plane from the head to the stomach for subsequent PAS st aining. The findings in both groups were compared at the three endpoints. C ontrol embryos had neither tracheoesophageal nor notochord malformations. O n day 12, only 11/36 adriamycin embryos were normal; 7/36 had abnormal noto chords, 11/36 had EA, and 7/36 had both. The corresponding figures for 12.5 days were 12/27, 0/27, 7/27, and 8/27 and those for the day 13 7/23, 5/23, 3/23, and 8/23. The malformed notochords were thickened, bifurcated, or tr ifurcated in the sagittal plane. The simultaneous presence of notochord and esophageal malformations suggests a direct link between both defects, but our observation of isolated occurrence of both shows that they reflect two expressions of the profound disturbance of embryonic para-axial organizatio n responsible for the cluster of malformations rather than a cause-effect a ssociation.