Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and man-hours have been dedicated to animal-based discovery and characterisation methods over decades. Identification of agents with teratogenic potential from the plethora of drugs and chemicals that human beings come into contact with in their everyday environment is crucial; although only some 10% of congenital anomalies are thought to be caused by teratogens, representing roughly one in every thousand live births, they compromise the quality of life for millions of individuals worldwide and cost billions of dollars in health care every year. Knowledge of the most hazardous substances would enable medical professionals and would-be mothers to minimize foetal exposure to them, helping to achieve the laudable goal of abolishing teratogen-induced malformations. The burden of this goal currently rests heavily upon animal-based testing. Tissue and organ cultures constitute the main basis of the in vitro systems currently being used, developed and researched in the field of teratogen testing, and may themselves be grouped into four categories : (a) Established cell lines (cell lines and embryonic stem cells), (b) Primary cell cultures, (c) non-eutherian embryos (both vertebrate and non-vertebrate), (d) Cultured mammalian embryos/primordia. Just less than 40% of substances that undergo teratogenicity testing in animals show teratogenic potential, which may be defined as positive, probable or possible. It is startling and disconcerting to realize that virtually all human teratogens so far identified have been discovered as a result of case reports and clinical series, i.e. despite animal studies, rather than because of them. The degree of disarray between animal species and the problematic nature of extrapolation to humans comes as no surprise when one considers the all the factors involved. In summary: susceptibility to teratogenesis varies between different species, different strains and among individuals; affected individuals frequently show different phenotypes, and all these aspects are influenced by genetic make-up, environmental factors, and metabolic and placental differences. [3] The major institutes/organisations working on reseach of teartogenesis in the world..jpg) .jpg) | Alternative methods are therefore an absolute necessity. Not only will the technology develop and the tests become more reliable, but the in vitro methods are already more reproducible, provide easier end-points, present no problems with respect to ‘route of exposure,’ placental transfer and metabolic differences, and are devoid of the plethora of confounding factors associated with the animal tests. Perhaps most importantly, the alternatives provide a means to establish vital mechanistic models of teratogenic action and reduce the human impact of the false positive and false negative results generated by unreliable and confusing animal models. As human cell culture technology improves, particularly regarding stem cells, new methods will undoubtedly evolve that will enable a closer in vitro approximation of in vivo human teratogenesis. We believe the information presented here provides a scientific basis for teratology research to move away from the old, inconsistent, futile animal models, through the adoption of now validated in vitro methods, towards the development of new, cheaper, easier, more reliable, more predictive in vitro screening techniques. [3]  |
