XENOPUS LAEVIS: A MODEL SYSTEM FOR THE STUDY OF EMBRYONIC RETINOID METABOLISM Ill. Isomerization and Metabolism of All-trans-retinoic Acid and 9-cis-Retinoic Acid and Their Dysmorphogenic Effects in Embryos during Neurulation

These investigations provide data pertaining to the metabolism and disposition of exogenous 9-cis-retinoic acid and all-trans-retinoic acid during neurulation in Xenopus embryos. Each isomer elicited malformations of the heart, eye, and brain, but-2-fold higher concentrations of all-trans-retinoic acid than 9-cis-retinoic acid were required to produce qualitatively and quantitatively sim-ilar dysmorphogenic effects. The dysmorphogenic effects of all-trans-retinoic acid could not be attributed to the isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. Evidence is provided that all-trans-retinoic acid and 9-cis-retinoic acid are both direct-acting dysmorphogens. After Xenopus embryos were exposed to all-trans-retinoic acid, elevated levels of 4-oxo-all-trans-retinoic acid, 4-oxo-1 3-cis-retinoic acid, all-trans-retinoyl--glucuronide, and 13-cis-retinoic acid were detected in the embryos, whereas embryonic levels of 9-cis-retinoic acid were actually slightly lowe