Effect of Retinoic Acid on Cleft Palate and Palatal Rugae Formation

Yang, Won Mo; Kim, Soo Il; Park, Kyung Ran; Lee, Young Ho; Kim, Won Sik

Abstract

For the study on the effect of retinoic acid on the formation of palatal rugae and the cleft palate, retinoic acid was administered orally 150mg/kg of body weight by gastric tube at GD 10.5 to Sprague-Dawley rats. The pregnant rats were sacrificed on GD 17.5 under ether anesthesia, and laparatomized. After removal of uterus, the number of pregnant sacs and fetuses were counted. The fetuses weighed, the MEE (medial edge epithelium) thickness measured and the mitotic figures counted after routine processing and H·E stain. All the palates were photographed, and the number of rugae & the rugal pattern analysed. TEM photographs of MEE cells were observed after routine processing. The results were as follows ; 1. Rat fetus body weight after retinoic acid treatment increased significantly compared with the control group. 2. Mitotic figures in the retinoic acid treated group increased significantly compared with control group. 3. In the retinoic acid treated group, 79.3% of fetuses had cleft palates. Among fetuses with cleft palates, complete cleft palates were 10.6%, incomplete cleft palate 89.4%. Incomplete clefts were of two types ; median type (cleft palate at the intermolar region) and soft palate type (cleft posterior to the 8th rugae). Median type was 64.6% and the soft palate type 35.4%. 4. 2.3% of the fetuses had the numerical anomaly of the palatal rugae in the control group, but that of retinoic acid treated group 87.7%. 5. 17.4% of palatal rugae of the control group was disrupted, but 100% of the retinoic acid treated group disrupted. 6. Rugal papillae were observed in the 15.1% of fetuses of the control group and 63.1% of fetuses of the retinoic acid treated group. 7. Longitudinal rugae were observed in 19% of fetuses of the retinoic acid treated group, but not in the control group. 8. In TEM photographs, cytoplasmic processes, intercellular space, and desmosomes decreased. Swelling of mitochondria & ER were also found in the retinoic acid treated groups. According to the above results, it appears that there is close relationship between palatal rugae and cleft palates, and that excess retinoic acid induces disruption of pattern and numerical variations of rat fetus palate rugae. Also retinoic acid has an inhibitory effect on the proliferation of medial edge epithelial cells of palatal shelves. The cleft palates may be induced by the above mentioned retinoic acid effects. But, the exact mechanisms of retinoic acid on cleft palate formation is not thoroughly known and should be further studied.