Abstract
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.