A dose-dependent transformation of embryotoxicity manifestations in the population of chick embryos

The world-wide and long-lasting stagnation in general incidence of inborn defects does not agree with the increasing impact of the environment. However, inborn defects alone are definitely a poor indicator of the reproductive risk being accompanied by much more frequent embryotoxicity manifestations -- death of the conceptus and growth retardation. Dose-dependent transformations of the embryotoxicity manifestations may explain both the stagnation in the incidence of inborn defects and the observed shifts in malformation spectra. An attempt was made to design a reliable experimental model to produce individual transformations resulting from the specific dose-response relationships inherited in teratogenesis. A population of chick embryos in different stages of development was exposed to increasing doses of cyclophosphamide, a model teratogen. All types of the transformations were recorded. Prenatal extinction of defective embryos, transition of single moderate defects to more severe and multiple malformations, as well as the changes in the incidence of certain types of defects exhibit a clear-cut positive dose dependence. Introducing this experimental system we will be able to study mechanisms underlying the particular transformations.