The effect of high doses of retinoic acid on prenatal craniofacial development in Macaca nemestrina.

Eight pregnant Macaca nemestrina were administered from 7.5 to 10 mg/kg retinoic acid by mouth from day 20 to 44 of gestation. All fetuses exhibited craniofacial abnormalities. The craniofacial complex was studied in detail utilizing gross photography, silver nitrate impregnation, radiography, alizarin staining, and histologic processing. Nearly all the bones of the craniofacial complex were affected; the zygomatic bone and the mandible were most severely altered. Premature fusion of the coronal suture occurred in all the specimens, and there was a clockwise rotation of the craniofacial complex on right lateral view. In general, the bones of the affected fetus were smaller and less well developed than in the control specimen. The abnormal specimens in the present investigation resembled the Treacher-Collins syndrome in humans, and may be the result of defective neural crest cell migration in the first and second branchial arches.