Biological Concerns on the Selection of Animal Models for Teratogenic Testing

During pregnancy fetus can be exposed to a variety of chemicals which may induce abortion and malformations. Due to the amounts of new substances coming into the market every year, a high demand for a rapid, reliable, and cost-effective method to detect potential toxicity is necessary. Different species have been used as animal models for teratogen screening, most of them sharing similar development processes with humans. However, the application of embryology knowledge to teratology is hampered by the complexity of the reproduction processes.The present chapter outlines the essential development periods in different models, and highlights the similarities and differences between species, advantages and disadvantages of each group, and specific sensitivities for teratogenic tests. These models can be organized into the following categories: (1) invertebrate species such Caenorhabditis elegans and Drosophila melanogaster, which have become ideal for screening simple mechanisms in the early periods of reproductive cycle, allowing for rapid results and minor ethical concerns; (2) vertebrate nonmammalian species such Xenopus laevis and Danio rerio, important models to assess teratogenic potential in later development with fewer ethical requirements; and (3) the mammalian species Mus musculus, Rattus norvegicus, and Oryctolagus cuniculus, phylogenetically more close to humans, essential to assess complex specialized processes, that occur later in development.Rules for development toxicology tests require the use of mammalian species. However, ethical concerns and costs limit their use in large-scale screening. By contrast, invertebrate and vertebrate nonmammalian species are increasing as alternative animal models, as these organisms combine less ethical requirements, low costs and culture conditions compatible with large-scale screening. In contrast to the in vitro techniques, their main advantage is to allow for high-throughput screening in a whole-animal context, not dependent on the prior identification of a target. In this chapter, the biological development of the animals most used in teratogenic tests is adressed with the aims of maximizing human translation, reducing the number of animals used, and the time to market for new drugs.