Lessons from Studies in Animals for the Evaluation of Human Risk from Teratogenic Agents

Abstract

In order to achieve meaningful results a knowledge of the distribution and fate of potentially teratogenic agents in both man and the experimental animal model used is essential. Of equal importance is a detailed knowledge of the stage of embryonic development at which treatment is applied and an appreciation of the placental system which is functional at the time of treatment. Before a working placental system involving direct exchange of solutes between the maternal and embryonic blood streams occurs, a beating heart must perfuse the extraembryonic membranes of the conceptus. Before this ‘haemotrophic’ phase the embryo survives by the uptake and intracellular breakdown of uterine secretions and decidua in the extraembryonic tissue - the so called stage of histiotrophic nutrition. The switch over from one to the other mode of embryonic nutrition takes place at different times in various species and this may lead to an altered teratogenic response. Whole embryo culture as well as isolated embryonic organ and tissue culture may therefore be of further help in assessing teratogenicity. It should be remembered that pharmacologically active agents may act independently on the mother, fetus, and fetal membranes thus considerably complicating the in vivo picture.