Craniofacial dysmorphogenesis following hypervitaminosis A in mice.

Malformations of the temporomandibular joint (TMJ), zygomatic arch, middle ear ossicles, and mandibular musculature following hypervitaminosis A were described in fetal mice. Pregnant mice (Mus musculus) were each given a 0.2-ml solution of corn oil containing 10,000 IU of retinol palmitate by gavage on day 8.7. Thirty-eight fetal heads were collected and hemisected. The left hemiheads were serially sectioned, stained, and examined histologically. Right halves were cleared and double-stained with alizarin red and alcian blue. The craniofacial morphologies of the test mice were found to vary from normal to maximally involved (feature unidentifiable) even among littermates. Both inter- and intralitter variation were discussed. Errors in chondrogenesis were determined to have produced the variety of dysmorphologies observed. Changes in Meckel's cartilage affected both the TMJ and ossicles; the presence of ectopic cartilages affected the zygomatic arch; and the musculature was affected secondary to skeletal system changes. Several modes of vitamin A interference leading to craniofacial dysmorphogenesis have been proposed in the literature. It was determined that proposals implicating altered cellular differentiation were the most compatible with the in vivo data recorded here and elsewhere.