Analysis of the development of normal foregut and tracheoesophageal fistula in an adriamycin rat model using three-dimensional image reconstruction.

To examine the developmental process of the normal trachea and esophagus and their maldevelopment leading to tracheoesophageal fistula (TEF), we performed three-dimensional (3-D) image reconstruction of the developing foregut in normal and adriamycin (ADM)-induced TEF rats. Microscopic images of serial sections of embryos from seven normal and 14 ADM-treated rats killed every half a day after 11-14 days' gestation were traced and reconstructed using a 3-D construction imaging system (TRI, RATOC System Engineering, Tokyo, Japan). In the normal embryos, the lung bud appeared just below the pharyngeal foregut on day 11 and it elongated caudally to shape into the trachea as they grew. A 'tracheoesophageal septum" did not emerge. In the TEF embryos, although the lung bud appeared in a similar position on day 11, the trachea and esophagus did not separate and only a common foregut tube elongated caudally, then bilateral bronchial primordia emerged directly from it. Furthermore, abnormal development of the notochord was evident, being retarded in separation from the foregut, finally descending along a more ventral course and bending sharply around the level of the bifurcation. Microscopically, less mesenchymal cellularity around the foregut was noted in the TEF embryos. The trachea seemed to be formed only by caudal elongation of the lung bud in the normal embryos. In the ADM-induced TEF embryos, the upper foregut appeared to develop only into the trachea, and this maldevelopment may be implicated in the abnormal interaction between the foregut and the surrounding mesenchyme.