Cardiac outflow tract septation process in the mouse model of transposition of the great arteries.

It has been reported that all-trans retinoic acid induces transposition of the great arteries (TGA) at 80-90% in ICR mice. The authors revealed that retinoic acid affects the initial formation of the conus cushions leading to a loss of spirality in the cardiac outflow tract. However, the aberrant process of septation has not been precisely defined. In this study, we observed the hearts of live embryos using a video system followed by scanning electron microscopic examination. First, we found that, in the retinoic acid-treated embryos, the proximal outflow tract cushions, in addition to hypoplasia and dysplasia, did not establish the continuity with the distal outflow tract cushions and could not contribute to the outflow septation. Second, the distal outflow tract did not rotate counter-clockwise, retaining the outflow septum anlage in the superoinferior position. Third, a tongue-like mesenchymal tissue had developed on the right anterior rim of the muscular interventricular septum and was incorporated into the interventricular septum. Altogether, these processes contributed to establishing a reversed relationship between the outflow septum anlage and the ventricular septum anlage. On the other hand, right-ward deviation of one or both of the distal outflow tract cushions, relative to the mesenchymal tissue, gave rise to variable degrees of overriding of the pulmonary artery orifice. We conclude that, due to hypoplasia and dysplasia of the proximal outflow tract cushions and lack of distal outflow tract rotation, the outflow septum anlage took an inverted relationship with the ventricular septum anlage. Various types of rightward shift of the outflow tract cushions produced a morphological spectrum of TGA-type cono-truncal anomalies.