Genetic determinants of teratogen-induced abnormal development in mouse and rat embryos in vitro.

Abstract

The response of an embryo to a teratogenic treatment is often critically dependent on its genetic makeup. However, in conventional in vivo studies of gene-teratogen interactions it may be difficult to distinguish between the effects of genes that are carried by the embryo and those that are carried by the mother. It is likewise not easy to determine whether an observed interaction is between a particular gene and the parent compound administered, or whether it is with a metabolite that has been generated by the maternal system. The use of whole rodent embryo culture offers certain advantages in the study of gene-teratogen interactions. Not only can the effects of metabolism and the maternal genotype be more carefully controlled, but the stage of development at which embryos of different genotypes are exposed can be matched. Rodent whole embryo culture has been used to a limited extent to study interactions between single gene mutations and teratogenic treatments, variations in responses of different strains to teratogens, as well as species differences in response to teratogens. These studies point to the need to precisely control the stage of development at the time of treatment in order to be able to make valid comparisons. But, even more important, they highlight the versatility of the whole embryo culture technique, and underscore the need for its wider use in evaluating the relative contribution of genes and environment to abnormal embryonic development.