Etretinate-induced malformation of the first two branchial arches: differential staining and microdissection study of embryonic cartilage.

Malformations of the cranial base, temporal bone and middle ear were induced in the offspring of Sprague-Dawley rats by a single intraperitoneal injection of 10-30 mg/kg etretinate (Tigasone) at days 8.5-10.5 of gestation. By differential staining of the embryonic craniofacial cartilage and bone, and microdissection of the otomandibular complex, the induced malformations were studied specifically. Defective formations of Meckel's cartilage and the cartilaginous skull base were found to be prominent features of the malformation. The malformation included defective middle-ear ossicles; especially the malleus and incus were fused with a shorter than normal long process and manubrium. In conjunction with the distal part of Meckel's cartilage, mandibular micrognathia was observed. All of the malformed tissues are derivatives of the first and second branchial arches. The teratogenically induced defects in the rat embryos show some similarities to the clinical syndromes of the first and second branchial arches in man.