The use of model lower organisms such as C. elegans (a nematode worm) and Drosophila melanogaster (the fruit fly) that contain well-defined and conserved genes shown to be involved in development has led to the proposal that perturbations in specific conserved pathways could serve as preliminary screens for developmental toxicants (Daston & McNamee, 2005; NRC, 2000). Research is still needed to confirm the usefulness of, and to develop, methods based on this approach.
Progress in the elucidation of the gene regulatory networks (GRNs; large networks of regulatory genes) that control development of the sea urchin embryo are being used to understand cell fate and embryo development at the molecular level (Ben-Tabou de-Leon & Davidson, 2007; Davidson, et al., 2002; Oliveri & Davidson, 2004). The architecture of this regulatory network "reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time" (Davidson, et al., 2002).
GRNs involved in the processes of embryonic cell specification and differentiation are being identified and used in a systems biology approach to understand developmental biology and toxicology. Cummings & Kavlock (2005) proposed this approach for identifying mechanisms of chemical toxicity to the developing embryo. Anderson, et al. (2005), described a systems biology approach for dose-response modeling for reproductive toxicology, as well as techniques to develop and convert cellular signaling network data into mathematical models. The models could be used to predict the shapes of dose-response curves for the effects of chemicals on cellular signaling networks during development.
The European Commission ReProTect project is a consortium of 32 EU organizations working to identify relevant mechanisms and develop in vitro test batteries and testing strategies that can identify chemicals hazardous to mammalian reproduction.
Information on these and other emerging research, methods, and policies for reproductive and developmental toxicity testing will be provided on AltTox.org in the future; please check back again.
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