Importance of Development of Ecotoxicogenomics in Understanding Molecular Mechanisms of Chemicals in Developing Animals

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  • IGUCHI Taisen
    National Institutes of Natural Sciences, National Institute for Basic Biology, Okazaki Institute for Integrative Bioscience

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  • 内分泌撹乱化学物質問題と健康リスク　　内分泌かく乱物質問題の解明のためのＥｃｏｔｏｘｉｃｏｇｅｎｏｍｉｃｓの重要性
  • ナイブンピカク ラン ブッシツ モンダイ ノ カイメイ ノ タメ ノ Ecotoxicogenomics ノ ジュウヨウセイ

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Developing organisms are sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in reproductive as well as nonreproductive organs, including persistent molecular alterations. Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans, some of which exhibit estrogenic or anti-androgenic activity by binding to estrogen or androgen receptors. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, should be identified to understand the molecular basis of estrogenic activity during embryonic development. To understand molecular mechanisms of estrogenic chemicals in developing organisms, we identified estrogen-responsive genes using cDNA microarrays and a quantitative reverse transcriptase-polymerase chain reaction, and genes related to estrogenindependent vaginal changes in mice induced by estrogens during a critical window. We also analyzed genes in Xenopus laevis embryos related to abnormalities induced by estrogenic chemicals using cDNA microarrays. Estrogen receptors and other steroid hormone receptors were cloned in various species, including the American alligator, crocodile, Florida red-bellied turtle, Silurana tropicalis, roach, Fundulus and mosquito fish. An environmental androgen, trenbolone, was found to induce persistent changes in the gonopodium and ovotestis in mosquito fish. In Daphnia magna, juvenile hormone agonists induce the production of male offspring. Tributyltin (TBT) induces imposex in rockshell through retinoid X receptor (RXR) activation. Microarray technology is a powerful tool for understanding the molecular mechanism of receptor-mediated toxicology in various animal species. Ecotoxicogenomics is a multidisciplinary field concerned with elucidating how the entire genome is involved in the biological response of wild animals exposed to environmental toxicants and stressors. Ecotoxicogenomics combines information from studies of genomic-scale mRNA profiling by microarray analysis (transcriptomics), protein profiling (proteomics), metabolite profiling (metabolonomics) and computational models to understand the roles of gene-environment interaction in the chemical toxicity. To understand the molecular mechanism of chemicals in developing wildlife, the establishment of ecotoxicogenomics is essential in the near future.

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