In vitro testing of teratogenic agents using mammalian embryos

The need for efficient methods to screen new chemicals, drugs, and environmental pollutants for their teratogenic activity is obvious. The method currently available, ie, pregnant-animal testing, is of considerable value but there are certain drawbacks which prevent reliance on this method alone as the predictive device. Nutritional state of the dam, variability in the developmental age of embryos from litter to litter and even within the same litter, metabolic differences between species, placental function, and a host of other factors must be taken into account before data obtained from animal testing can be logically extrapolated to human situation. Many of these variables are either eliminated altogether or at least can be controlled by the use of tissue culture techniques. After surveying a variety of in vitro systems, it is our opinion that organ culture, whole embryo culture, and a combination of the two offer at present the best potential for screening of suspected teratogens. These culture techniques provide a much better simulation of in vivo situations than isolated cells grown as monolayers. Among other advantages, these procedures allow one to exercise control over the effective concentration of the suspected teratogen to which an embryo is exposed and also the duration of this exposure. Since maternal metabolism or modification of the drug is routinely eliminated in these experiments, there is a need for exploring the use of drug-metabolizing preparations as additives to the culture medium. The choice of limb bud in the screening system is promising since during its development, the limb progresses through a succession of embryonic processes that are generally relevant to other organ systems as well. Hence, such a screening system may not only predict teratogenicity but also provide insight into the mechanisms by which a test chemical is teratogenic.