Hypoplasia of cushion ridges in the proximal outflow tract elicits formation of a right ventricle-to-aortic route in retinoic acid-induced complete transposition of the great arteries in the mouse: scanning electron microscopic observations of corrosion cast models

Abstract

Background: The major morphologic change associated with retinoic acid (RA)-induced complete transposition of the great arteries (TGA), a congenital malformation of the heart, was investigated in a mouse model in which TGA was found in 80% of surviving fetuses.

Methods: Corrosion casts of embryonic hearts with or without prior exposure to retinoic acid were observed under a scanning electron microscope.

Results: In control hearts, indentations caused by expanded parietal and septal ridges in the outflow tract established right ventricle-to-left ventral pulmonic and left ventricle-to-right dorsal aortic routes before the aorticopulmonary septum completion. In RA-treated hearts, indentations of proximal regions of the parietal and septal ridges were small in the proximal outflow tract, whereas those in the distal regions developed well. These morphological features in the RA-treated hearts elicited right ventricle-to-right ventral aortic and left ventricle-to-left dorsal pulmonic routes in the TGA morphology.

Conclusions: Hypoplasticity of the proximal regions of parietal and septal ridges in the outflow tract is one of the primary morphological abnormalities of the RA-induced TGA.