Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. 
Though very effective, it is teratogenic if administered during pregnancy, and 
its teratogenic effect may be related to the normal activity of retinoids as 
signalling molecules in the embryo. Although its exact mechanism of action is 
unknown, it has been suggested that it causes its characteristic pattern of 
defects that includes heart defects, by inhibiting the migration of neural crest 
cells. However, other effects on cells are known. We studied early cardiac cell 
proliferation using incorporation of bromodeoxyuridine (BrdU) and detection with 
a monoclonal anti-BrdU. Proliferation in heart tissue of whole embryo cultures 
was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level 
in myocardium. We studied its effects in culture on precardiac explant 
development in the absence of the neural crests. Culture of precardiac 
mesodermal-endodermal explants revealed that development of heart vesicles from 
the mesoderm was little affected, but the development of heartbeat was inhibited 
depending on dose in the 10(-5) to 10(-7) M range. The effect on development of 
contractions was augmented in the presence of serum; it could be duplicated by 
all-trans-retinoic acid, and it was reversible. Synthesis of the alpha-actin 
isotype, analyzed by isoelectric focusing, was found to be inhibited or delayed. 
The results suggest multiple effects of retinoids on growth, morphogenesis, and 
differentiation of early cardiac tissue, and are discussed in relation to the 
potential role of retinoids in early embryogenesis.