The effect of excess vitamin A on the development of rat embryos in culture

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Abstract
Primitive streak stage rat embryos were cultured in serum containing added vitamin A alcohol at concentrations ranging from 0.5 to 20μg/ml. At the higher concentrations there was an overall growth retardation, and differentiation was inhibited. This was thought to be due to inhibition of DNA synthesis. At 0.5 μg/ml the embryos developed abnormally in a manner similar to that previously seen in vivo. This result, which was supported by an ultrastructural study, provides evidence that the teratogenic effects of vitamin A are due to a direct action on the embryos. Comparison of embryonic development in vitro at different concentrations of vitamin A with the results obtained in vivo suggests that in the latter, only a very small proportion of the amount injected was reaching the embryos in an active form. The maternal factors involved are discussed, and excess vitamin A is defined as an excess of free and non-specifically bound retinol. The levels of vitamin A which affected differentiating embryos in vitro are lower than the minimum levels previously shown to affect differentiated tissues. This suggests that relatively minor increases in serum levels during pregnancy may cause malformations without affecting the maternal organism. Since raised serum vitamin A levels have been shown to be associated with impaired liver function in man, these factors may be significant in human teratogenesis.