Abnormal ventricular looping and abnormal laterality of the atrial chambers are the main morphogenetic mechanisms of cardiac lesions in cultured rat embryos treated with retinoic acid.

To establish the early morphogenetic mechanism in retinoid induced cardiac lesions, we investigated the morphology of the heart in cultured rat embryos treated with retinoic acid (RA) at 9.0 and 9.5 days post coitum (d.p.c). Wistar rat embryos were treated with RA (2 x 10(-7) M) for 6 hours from the embryonic day equivalent of 9.0 or 9.5 d.p.c. After further culture in an RA free medium for 2.5 days, embryos were fixed and examined with a stereomicroscope and a scanning electron microscope. Sixty three embryos were treated at 9.0 d.p.c., 14 embryos were treated at 9.5 d.p.c. and 30 embryos were used as control. Abnormal ventricular looping was seen in 31 embryos (49.2%) from the group treated at 9.0 d.p.c., and isomerism of right appendages occurred in 15 (23.8%). Embryos treated with RA at 9.5 d.p.c. showed a low incidence of abnormal ventricular looping (14.3%). We could summarize those abnormal looping as three variants of each looping. The mildest form was hypoplasia of the right ventricle observed in 20 cases. Both the right and left ventricles in the second variant were shifted far to the left or right (10 cases). The third variant was a heart with generalized hypoplasia of both ventricles (3 cases). The incidence of branchial arch anomalies was higher at 9.5 d.p.c. than at 9.0 d.p.c. (71.4% and 30.2%, respectively). Abnormalities in the ventricular looping and the atrial laterality at 9.0 d.p.c. suggest that RA induces derangement in the development of laterality, while at 9.5 d.p.c., the abnormality of the migration of neural crest cells is the principal mechanism.