Correlations between conceptal concentrations of all-trans-retinoic acid and dysmorphogenesis after microinjections of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinoyl-beta-glucuronide, or retinol in cultured whole rat embryos.
Retinol (4,000 ng/ml), all-trans-retinoyl-beta-glucuronide (4,000 ng/ml), and 13-cis-retinoic acid (1,500 ng/ml) each produced dysmorphogenic effects qualitatively similar to those elicited by 250 ng/ml of all-trans-retinoic acid after microinjections of the respective individual retinoids into the amniotic cavities of cultured whole rat embryos. Subsequent HPLC analyses of the cultured whole conceptuses, embryos proper, yolk sacs, and culture media (24 hr after microinjections) indicated that conceptal biotransformation of each of the retinoids had occurred during the culture period. All-trans-retinoic acid was present in the embryos proper at quantitatively similar concentrations (20-100 nM) after microinjections of the selected quantities of each of the microinjected retinoids: retinol, all-trans-retinoyl-beta-glucuronide, 13-cis-retinoic acid, or all-trans-retinoic acid. The results suggested that all-trans-retinoic acid acted as an ultimate dysmorphogen for the retinoids tested with respect to the anomalies monitored in the embryo culture system.
Kraft
J C
JC
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
Juchau
M R
MR
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015474:Isotretinoin / Q000032:analysis* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000633:toxicity; D014801:Vitamin A / Q000032:analysis* / Q000633:toxicity
D014801:Vitamin A; C026787:retinoyl glucuronide; D014212:Tretinoin; D015474:Isotretinoin