Apoptosis in tracheoesophageal embryogenesis in rat embryos with or without adriamycin treatment

Purpose: The aim of this study was to determine whether apoptosis participa tes in separation of the foregut into trachea and esophagus and to evaluate the potential role of apoptosis in the development of esophageal atresia a nd tracheoesophageal fistula (EA + TEF) induced by Adriamycin. Methods: Timed-pregnant rats were injected daily with either saline or Adri amycin (2 mg/kg) intraperitoneally on days 6 to 9 of gestation. Paraffin se ctions were prepared from 31 experimental and 31 control embryos at days 12 and 13 of gestation. Condensed nuclei were identified on the paraffin sect ions using the TUNEL method. Apoptosis was quantified by counting the posit ively stained cell nuclei in transverse sections of embryos. Results: In day 12 control embryos the number of apoptotic nuclei in both l ateral ridges of the foregut was high (15.67 +/- 1.38) but relatively low ( 4.17 +/- 0.80) in Adriamycin-treated embryos (P<.0001). In day 13 Adriamyci n-treated embryos, the number of apoptotic nuclei in the region of the uppe r esophageal pouch was extremely high (23.78.5 +/- 2.20) compared with no d etectable apoptotic nuclei in the control embryos. Conclusions: Apoptosis is required for normal tracheoesophageal embryogenes is and may be an important mechanism to be involved in the embryological de velopment of esophageal atresia and tracheoesophageal fistula. Copyright (C ) 1999 by W.B. Saunders Company.