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Application of Ecotoxicogenomics for Studying Endocrine Disruption in Vertebrates and Invertebrates

机译:生态毒理基因组学在研究脊椎动物和无脊椎动物内分泌干扰中的应用

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摘要

Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans. Developing organisms are particularly sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in both reproductive and nonreproductive organs, including persistent molecular alterations. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, need to be identified for investigators to understand the molecular basis of estrogenic activity during embryonic development. For investigators to understand molecular mechanisms of toxicity in various species, toxicogenomics/ecotoxicogenomics, defined as the integration of genomics (transcriptomics, proteomics, metabolomics) into toxicology and ecotoxicology, need to be established as powerful tools for research. As the initial step toward using genomics to examine endocrine-disrupting chemicals, estrogen receptors and other steroid hormone receptors have been cloned in various species, including reptiles, amphibians, and fish, and alterations in the expression of these genes in response to chemicals were investigated. We are identifying estrogen-responsive genes in mouse reproductive tracts using cDNA microarrays and trying to establish microarray systems in the American alligator, roach, medaka, and water fleas (Daphnia magna). It is too early to define common estrogen-responsive genes in various animal species; however, toxicogenomics and ectotoxicogenomics provide powerful tools to help us understand the molecular mechanism of chemical toxicities in various animal species.
机译:释放到环境中的化学物质可能破坏野生动物和人类的内分泌系统。发育中的生物对雌激素化学物质特别敏感。在发育的关键时期暴露于雌激素或雌激素化学物质会引起生殖器官和非生殖器官的持续变化,包括持续的分子变化。因此,需要确定雌激素反应性基因和各种动物的关键发育窗口,以便研究者了解胚胎发育过程中雌激素活性的分子基础。为了使研究人员了解各种物种的毒性分子机制,需要建立毒理基因组学/生态毒理基因组学(定义为将基因组学(转录组学,蛋白质组学,代谢组学)整合到毒理学和生态毒理学中)作为强有力的研究工具。作为使用基因组学检查破坏内分泌的化学物质的第一步,已将雌激素受体和其他类固醇激素受体克隆到各种物种中,包括爬行动物,两栖动物和鱼类,并研究了这些基因对化学物质的响应变化。我们正在使用cDNA微阵列识别小鼠生殖道中的雌激素反应基因,并试图在美洲短吻鳄,蟑螂,和跳蚤(Daphnia magna)中建立微阵列系统。在各种动物物种中定义常见的雌激素反应基因为时尚早。但是,毒物基因组学和外毒物基因组学提供了强大的工具,可以帮助我们了解各种动物化学毒性的分子机制。

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