Alterations in palatal ruga patterns in Jcl:ICR mouse fetuses from dams treated with all-trans-retinoic acid

Pregnant Jcl:ICR mice were orally given all-trans-retinoic acid (RA) at dose levels from 0.08 to 80 mg/kg once at days 10.5, 11.5, or 12.5 (vaginal plug = day 0) of gestation. The dams were sacrificed at day 18.5 of gestation, and the fetuses were dissected. After fixation in Bouin's solution, the fetal palates were observed under a dissecting microscope. Pattern alterations rare in the control fetuses were shortness, fusion, maldirection, trirugal malalignment, modified cross, and cross. These alterations were defined as abnormalities. Cleft palate was induced at dose levels of 20 mg/kg and above. At each treatment day, the total incidence of abnormal rugae increased from the dose of 0.3 or 0.6 mg/kg, dose-dependently. Although missing ruga-8 was a common pattern alteration in vehicle controls, its incidence increased dose-dependently. The incidence of supernumerary posterior to ruga 3 increased dose-dependently after treatment at day 11.5 or day 12.5 of gestation, however the increase was not observed after treatment at day 10.5 of gestation. These findings indicate that the abnormalities of ruga, missing ruga-8 and supernumerary posterior to ruga 3 are very sensitive indicators of teratogenicity of RA.