Teratogenicity of benzoic acid derivatives of retinoic acid in cultured mouse embryos.
Isotretinoin (13-cis-RA) is a human teratogen and mouse embryos exposed to 13-cis-RA in vivo exhibit many of the same defects as humans. Early postimplantation mouse embryos exposed to 13-cis-RA in culture exhibit developmental alterations of the visceral arches, similar to those seen after in vivo exposure. Certain benzoic acid derivatives of retinoic acid have been shown to possess activity equal to or greater than retinoic acid in several in vitro systems. This study examines the teratogenic effects of some of these retinoids on mouse embryos in vitro. Day 8 CD-1 mouse embryos were cultured for 48 hours in the presence of these benzoic acid derivatives. With the exception of Ro-15-0778, all compounds produced visceral arch malformations similar to those seen in embryos exposed to 13-cis-RA, but at dramatically different effective concentrations. Extremely low concentrations of the retinoic acid-related compounds tested appear to have detrimental effects on embryonic development and these compounds may be poor candidates for therapeutic use.
Goulding
E H
EH
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Jetten
A M
AM
Abbott
B D
BD
Pratt
R M
RM
D000818:Animals; D001565:Benzoates / Q000633:toxicity*; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice / Q000196:embryology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000633:toxicity*; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000633:toxicity
D001565:Benzoates; D013723:Teratogens; D014212:Tretinoin