Sensitive stages and dose-response analyses of palatal slit and cleft palate in C57BL/6 mice treated with a glucocorticoid.

Abstract

C57BL/6 mice were treated subcutaneously with triamcinolone acetonide in a single dose of 2.5-15.0 mg/kg once on days 6-15 of pregnancy (vaginal plug = day 0) and the palate of their fetuses was examined at term. The sensitive stages of palatal slit and cleft palate induction were studied and dose-response relations on days 9 and 12 of pregnancy were analyzed by the log-probit transformation method and compared. The test of significant increase in the frequencies of palatal slit and cleft palate showed that the sensitive period of palatal slit began earlier and ended later than that of cleft palate. On day 9 of pregnancy, the slope of the palatal slit response was similar to that of the cleft palate response, but the median effective dose of the former was lower than that of the latter. The slope of the palatal slit response was similar on days 9 and 12; however, the median effective dose was significantly greater on day 9. By contrast, the slope of the cleft palate response on day 12 was significantly different from that on day 9. The results of these dose-response analyses suggest that the underlying mechanism may be the same in palatal slit induction on days 9 and 12 and in cleft palate induction on day 9; the mechanism underlying the cleft palate response on day 12 is different from that of the other three responses, and there is more than one mechanism for cleft palate induced by triamcinolone.