ALTERED DISTRIBUTION OF COLLAGEN TYPE-I AND HYALURONIC-ACID IN THE CARDIAC OUTFLOW TRACT OF MOUSE EMBRYOS DESTINED TO DEVELOP TRANSPOSITIONOF THE GREAT-ARTERIES

Complete transposition of the great arteries (TGA) is inducible by tre atment with all-trans retinoic acid in the ICR mouse. In this model, h ypoplasia and dysplasia of the proximal outflow tract cushion tissue l ead to non-spiral septation. In order to evaluate the effect of retino ic acid on the extracellular matrix of the cardiac outflow tract, we e xamined the distribution of collagen type I and hyaluronic acid, immun ohistochemically, on days 8-9 of gestation. In controls, collagen type I fibrils ran mainly in a radial direction, extending towards the end ocardium in the cardiac jelly of the proximal outflow tract. Also, a p air of longitudinal fiber bundles were formed stretching to the distal outflow tract. As for hyaluronic acid, intense staining was observed in the submyocardial and intermyocardial space of the outer curvature of the heart. On the other hand, in retinoic acid-treated embryos, the submyocardial radial fibrils or longitudinal fiber bundles of collage n type I were diminished, and irregular and dense deposits of collagen type I were observed along the endocardium. Furthermore, hyaluronic a cid showed a loss of differential localization between the outer and i nner curvature. Instead, irregular and intense staining was observed u niformly along the outflow myocardium. Thus, retinoic acid appeared to have perturbed the differentiation in the proximal outflow tract caus ing an altered organization of multiple extracellular matrix molecules , including collagen type I and hyaluronic acid, which led to an abnor mal molecular network of the cardiac jelly in the cardiac outflow trac t, abnormal septation and, further, to TGA or TGA-type anomalies.