Retinoic acid-induced heart malformations in the hamster

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Abstract

In order to determine the effect of retinoic acid on the developing mammalian heart, pregnant golden Syrian hamsters were given single doses of 80 mg/kg of the teratogen by gavage, at various times in gestation. Examination of the surface features of hearts from near-term fetuses was followed by microdissection to reveal internal cardiac structures. This has proven to give more reliable results than other methods of determining congenital heart malformation. The results of the study demonstrate that retinoic acid is a potent cardiac teratogen capable of inducing high frequencies of heart abnormalities in a reproducible fashion. The highest rates of malformation resulted from maternal treatment on day 7 (69%), 8 (74%), and 9 (30%) of gestation. Ventriculo-bulbar malformations including double outlet right ventricle, complete transposition, and an overriding aorta complex were the most commonly seen abnormalities. The findings support the hypothesis that these abnormalities are not entirely discrete entities but are instead part of a single spectrum of malformation.

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