Experimental craniofacial malformations induced by retinoids and resembling branchial arch syndromes

A syndrome which showed similarities to human branchial arch syndromes could be induced in Sprague-Dawley rat embryos by exposing them to retinoids prenatally. Treatment of pregnant rats with 40 mg/kg retinoic acid or 10 mg/kg etretinate on pregnancy day 8.5-9 resulted in craniofacial defects in 100% of the embryos. A scanning electron microscopic investigation of the early stages in the development of these malformations showed abnormal skull form, disorganised surface epithelium with "cell blebbing", lateral facial clefts, facial fistulas, narrowed skull-base and reduced size of the nasal and maxillary complexes. Histological examination confirmed these findings and supported the hypothesis that a main reason for this syndrome is hindrance of migration of the cranial neural crest cells to the facial processes during early craniofacial formation.