Ultrastructural observations on the development of triamcinolone-induced cleft palate in hamsters

Cleft palate was induced in fetuses by administration of triamcinolone to pregnant hamsters. Twenty hours after treatment, alterations were seen at the epithelial-mesenchymal interface in the prospective fusion epithelium of the vertical shelf. The alterations included contacts between the epithelial and mesenchymal cells, and disruptions in the continuity of the basal lamina. Thirty-two hours after triamcinolone treatment, the basal epithelial cells in some of the reorienting palatal shelves were necrotic. When compared with normal cells, the drug treated necrotic cells were lighter in appearance due to reduced polyribosomes; they also lacked lysosomes. In other reorienting shelves, the basal cells were lost and the epithelial continutity was maintained by the superficial cells. The alterations at the epithelial-mesenchymal interface, and the necrotic changes in the basal cells, became more severe with delayed horizontal reorientation of the palatal shelves. The necrotic debris was cleared by macrophages. At a later stage, the opposing epithelia of the horizontal shelves did not fuse but underwent stratification. It appears that triamcinolone induces alterations at the epithelial-mesenchymal interface, and inhibits the normal process of protein synthesis in the epithelial cells during palatogenesis. This, along with delayed differentiation of mesenchymal cells, distrupts the timing of coordinated development of the palatal tissues. These changes are associated with a delay in the reorientation of the palatine shelves, and cleft palate results.