DISTRIBUTION OF ALL-TRANS-, 13-CIS-RETINOIC AND 9-CIS-RETINOIC ACID 9O EHOLE RAT EMBRYOS AND MATERNAL SERUM FOLLOWING ORAL-ADMINISTRATION OF A TERATOGENIC DOSE OF ALL-TRANS-RETINOIC ACID

Maternal administration of 200 mg/kg all-trans-retinoic acid to rat em bryos at early limb stages of development (day 12 to day 13.5 post coi tum) results in limb reduction defects. In order to determine the dura tion of exposure of the embryo to raised levels of all-trans-retinoic acid, we have used high performance liquid chromatography to measure r etinoid levels at a series of time intervals following maternal admini stration on day 12.5 post coitum. Raised levels of all-trans-retinoic acid and 13-cis-retinoic acid were detectable in embryos after 30 min. , reached a peak at 2 hr, and had fallen sharply by 4 hr. 13-cis-Retin oic acid levels were undetectable after 4 hr, and all-trans-retinoic a cid levels after 8 hr. 9-cis-retinoic acid levels rose more slowly, we re less elevated, and fell more gradually than the other two retinoids . The retinoid profiles in maternal serum were similar. The results in dicate that induction of limb abnormalities by all-trans-retinoic acid in rat embryos is associated with a relatively short-term rise in emb ryonic retinoid levels.