Exogenous
retinoic acid has been found to be teratogenic in animals and man. Craniofacial defects induced by
retinoic acid have stimulated considerable research interest. The present report deals with scanning electron microscopical observations of the craniofacial region concurrent with histological examination of craniofacial dysmorphism induced in rat embryos following maternal treatment treated with varying dosages of
all-trans-retinoic acid (
tretinoin). Two groups of pregnant rats were treated with rat embryos exposed to
retinoic acid suspended in
corn oil (100 mg/kg b.w. on gestational day 11.5 and 50 mg/kg b.w. on gestational day 10, 11 and 12 respectively). A third group was treated with
corn oil (vehicle) while a fourth group remained untreated. A wide spectrum of
congenital abnormalities, including
exophthalmos,
microphthalmia and
anophthalmia, maxillo-mandibular
dysostosis,
micrognathia of both maxilla and mandible,
cleft palate, subdevelopment of ear lobe, preauricular tags and
macroglossia, were observed in the offspring of
retinoic acid treated animals. The abnormalities were both time and dosage dependent, and characteristic of
Treacher Collins syndrome when
retinoic-acid was administered on gestational day 11.5. In contrast, when
retinoic acid was administered were on gestational days 10-12, the defects were similar to those seen in the first and second pharyngeal arch syndrome, as well as in the oculo-auriculo-vertebral spectrum. Whereas our data support the hypothesis that
all-trans retinoic-acid disturbs growth and differentiation of several embryonic cell types essential for normal craniofacial development, its mechanism of action remains unclear.