All-trans-retinoic acid-induced variant patterns of palatal rugae in Crj:SD rat fetuses and their potential as indicators for teratogenicity.

We determined the critical period for cleft palate formation in the presence of all-trans-retinoic acid (RA) and defined anomalous patterns within the variants of palatal rugae. The total incidence of variant patterns of palatal rugae in rat fetuses treated with RA at 40 mg/kg on gestation days 13 and 14 dramatically increased with concurrent induction of cleft palate. Correspondence analysis connected the variant patterns of palatal rugae, such as median discontinuity, extra peaks, supernumerary ruga (extra type), shortness, fusion, and bifurcation, with cleft palate. Therefore, these variants were concluded to be anomalous. The incidence of the anomalous patterns of palatal rugae was about 10 times that of cleft palate, and consequently, these anomalies might be sensitive indicators of the teratogenicity of a chemical.