Gene expression profiling to examine the thyroid hormone-disrupting activity of hydroxylated polychlorinated biphenyls in metamorphosing amphibian tadpole

Abstract

Hydroxylated polychlorinated biphenyls are the metabolites produced from parent compounds by the drug-metabolizing enzyme cytochrome P450. These compounds are suspected to disrupt postembryonic neural development in the brains of mammals including humans. We studied the effects of these compounds on thyroid hormone function in the brain by using metamorphosing tadpoles of the African clawed toad (Xenopus laevis) as a model for mammalian postembryonic development. The metamorphosis assay revealed that these compounds inhibit thyroid hormone-induced metamorphosis. Genome-wide gene expression analysis in the brain following short-term exposure demonstrated that delayed metamorphosis could partially be caused by disruption of thyroid hormone-induced gene expression. Furthermore, we associated the terms of functional ontology with the genes, whose expression was disrupted by these compounds. We suggest that the use of a genome-wide analysis coupled with bioinformatics might provide an overview of the molecular mechanism underlying thyroid-disrupting activities in vivo. © 2011 Wiley Periodicals, Inc.