Rodent whole-embryo culture as a teratogen screening method

Postimplantation embryo techniques can sensitively detect compounds with adverse biological activity. The versatility of the in vitro embryo toxicity/teratogenicity screening assay has been augmented by the addition of adult hepatic metabolic activation systems, which influence the results for some compounds in the embryo culture system. In this assay, cyclophosphamide produces negative results without metabolic activation and positive results with activation; metabolic activation changes the results for cytochalasin D from positive to negative. Another improvement has been the evaluation of the embryo toxicity/teratogenicity of various water-immiscible solvents. As these studies revealed that sonicated corn oil/serum preparations were nontoxic at concentrations of up to 10% of the culture medium, these solvents can now be used to expose cultured embryos to water-insoluble compounds (e.g., chlorinated pesticides). This in vitro rodent whole-embryo culture makes it possible to investigate extremely rapid cell division and specific time-related morphogenic events. Because in vitro development so closely parallels that occurring in vivo, the in vitro embryo culture system appears to be particularly relevant for the detection of teratogenic and embryotoxic compounds. A variety of compounds have been assayed in vitro via a combination of metabolic activation system and/or water-insoluble chemical delivery systems. Correlation between the published results of the in vitro screening assay and the published results of in vivo embryo toxicology and teratology studies has been very good. However, most of the compounds used in in vitro testing have been strongly teratogenic, and little information is available on compounds that are not teratogenic in in vivo tests. There is also a good correlation between the concentrations of teratogenic agents that cause adverse effects in vitro and the in vivo teratogenic doses of these compounds.