Effects of 25-Hydroxy Vitamin D3 on the Incidence of Diphenylhydantoin Induced Cleft Palate in Mice
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Women who have epilepsy and who take the anticonvulsant diphenylhydantoin (DPH) during pregnancy produce infants that have an abnor-high incidence of cleft palate and other anomalies. DPH will induce cleft palates in laboratory mice exposed to the drug while in utero. It has been suggested that DPH may exert its teratogenic effect by interfering with Vitamin D metabolism. We tested the hypothesis that decreased concentrations of vitamin D could be secondary to treatment with DPH and could be related to the induction of cleft palates in mice. To do this we treated groups of pregnant mice with DPH or the combination of DPH and 25 hydroxycholecalciferol (25 hydroxy Vitamin D3) during the critical period of palatogenesis. Treatment with 25 hydroxycholecalciferol did not decrease the incidence of DPH-induced cleft palate. In fact, fetuses from mice treated with DPH and 25 hydroxycholecalciferol had an increased incidence of cleft palate as compared to fetuses from dams treated only with DPH. Treatment with the Vitamin D metabolite added to or potentiated the effect of DPH. This was further supported by the fact that dams given both compounds had significantly more dead fetuses than did dams given either the Vitamin D metabolite or DPH alone.