Maternal Hyperoxia Greatly Reduces the Incidence of Phenytoin-Induced Cleft Lip and Palate in A/J Mice

Abstract

The A/J mouse has been used to study the teratogenic affects of phenytoin. The developmental abnormalities produced in offspring of this model are similar to some of the malformations observed in cases of human "fetal hydantoin syndrome." Placing pregnant A/J mice in a hyperoxic chamber after phenytoin injection greatly reduces the incidence of phenytoin-induced cleft lip and palate. These results suggest that phenytoin may affect embryonic development indirectly by altering maternal physiology. This maternally mediated mechanism, and the protection against it afforded by hyperoxia, has general implications for the effects of maternal toxicity on teratogenesis.