Electron Microscopic Studies on the Effects of Retinoic Acid on Palatogenesis in Fetal Rats

Kim, Won Kyu; Woo, Bong Sik; Nam, Yong Seok; Paik, Doo Jin; Youn, Jeehee; Bae, Sung Man; Chung, Ho Sam

Abstract

Retinoic acid (RA) is widely used to treat the dermatologic disorders, such as acne and psoriasis, but its usage is limited because of teratogenic effects. Moreover, it is known that RA induces cleft palate by influencing epithelial differentiation and mesenchymal cells in palatine processes. We studied the ultrastructures of the epithelial and mesenchymal cells in rat palatine shelves treated with RA, in comparison with those of the normal developing rat. In this experiment, pregnant Sprague -Dawley rats were treated with 100 mg/kg of all -trans retinoic acid at day 10 of gestation. Pregnant rats were killed at 14 th and 16 th day of gestation. Fetuses were removed and palatine processes were dissected. The specimen were observed with a transmissiom electron microscope. The results were as follows. 1. Palatine epithelium of control rats was made up of two cell layers at day 14 of gestation, and that of RA treated rats consisted of multicellular layers. At the 16th day of gestation, many apoptotic bodies were observed in triangular area of the palatine epithelium of the control rat. In contrast, apoptotic cells were hardly observed in RA treated rats. 2. Mesenchymal cells of control rats contained cytoplasmic process, oval -shaped nucleus, well -developed rough endoplasmic reticulum, Golgi complex, and mitochondria. RA treated mesenchymal cells showed atrophied cisternae of Golgi complex, rough endoplasmic reticulum with sacculated, fragmented and ribosome detached cisternae, mitochondria with dissolved mitochondrial cristae, and multivesicular body. After RA exposure during palatogenesis, the frequency of apoptotic bodies was low in palatine epithelium, and mesenchymal cells were severely damaged. In conclusion, it is suggested the RA may induce direct cytotoxic effects on mesenchymal cells and influence normal apoptosis process in developing epithelium.