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Diagnosing Toxicant Specific Disruption of Sexual Development in Wild Fish using Metabolomics

使用代谢组学诊断野生鱼类性发育的有毒特异性破坏

基本信息

批准号：
NE/D002818/1
负责人：
Mark Viant
金额：
$ 27.35万
依托单位：
UNIVERSITY OF EXETER
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FD002818%2F1
关键词：
Diagnosing Toxicant Specific Disruption Sexual

项目摘要

Environmental monitoring is important for determining if man-made stressors, such as pollution and climate change, are damaging animals that live in our aquatic environment. Perhaps surprisingly, up to half of the water flowing in some UK rivers originates from the effluent of sewage treatment plants and this can affect the native wildlife. Several years ago we found that the reproductive systems in fish living in many UK rivers had been damaged by exposure to chemicals contained in the sewage treatment plant effluents that disrupt the body's sex hormone systems. Although scientists now have tools for determining if fish reproductive systems have been damaged, these generally involve killing the fish and examining dissected tissues, which is not ideal for extensive impact monitoring programmes. Also, the existing tools do not provide much information on the types of pollutants that are causing the damage.Such information would be very useful to environmental regulators,and could be used to help trace the source(s) of pollutant(s) and to help design strategies to remove these chemicals from the water before they damage fish and other animals. The aim of this research project is to develop and apply a new technology (called 'metabolomics') for assessing the health of fish by measuring large numbers of small molecules (called metabolites) in their blood and tissues. These measurements are so detailed that they can provide information on exactly which parts (or 'metabolic pathways') of the fish's reproductive system are damaged. This approach is now also being used successfully in hospitals to assess human diseases, and we will use it to look for unique patterns or 'signatures' in wild fish that would determine if they are damaged and if so by what types of pollutants in the river. To achieve this we will first need to expose fish (the roach, in which we have shown widespread sexual disruption) in the laboratory to single pollutants that are suspected to be involved with disruption of reproduction in wild fish, and measure the damage caused by each of these chemicals. These experiments will include short and long exposures of the fish, some of which will last for two years to accurately mimic real environmental scenarios. Then we will 'train' computers to recognize the specific patterns of pollutant-induced damage, and those computers will search for these patterns in the wild fish in much the same way they can search through genetic fingerprints to match those collected at a crime scene. Another advantage of 'metabolomics' is that unlike most existing environmental monitoring methods, it can be conducted rapidly using only a minute volume of blood taken from the fish, which can then be released back into the river. The final advantage is that the measurements of certain metabolites in the blood, particularly those called 'sex steroids', can tell us a lot about the fish's reproductive health, i.e., there is a close relationship between these molecular measurements and the overall fitness of the whole fish. The tools used in 'metabolomics' are more commonly associated with chemistry labs and include nuclear magnetic resonance spectroscopy and mass spectrometry. Also, because of the immense amount of data that will be produced, experts in mathematics will also be needed. Our multi-disciplinary team has expertise in chemistry, biology, toxicology and mathematics, and brings together scientists from the Universities of Birmingham and Exeter, as well as the Environment Agency, a Water company and a Mass Spectrometry company. Ultimately the results of this study will enable development of a more appropriate methodology and practical set of tools (called 'biomarkers') for end-users, which can contribute to environmental impact assessments and the regulation of discharges by the regulatory authorities. This will provide a more informed knowledge of the health of our rivers thus protecting our aquatic resources and biodiversity.

环境监测对于确定污染和气候变化等人为压力源是否正在损害生活在我们的水生环境中的动物非常重要。也许令人惊讶的是，英国一些河流中多达一半的水来自污水处理厂的废水，这可能会影响当地的野生动物。几年前，我们发现生活在英国许多河流中的鱼类的生殖系统受到了污染，原因是污水处理厂的废水中含有的化学物质破坏了人体的性激素系统。尽管科学家们现在有了确定鱼类生殖系统是否受损的工具，但这些工具通常涉及杀死鱼类并检查解剖组织，这对于广泛的影响监测项目来说并不理想。此外，现有的工具并不能提供太多关于造成损害的污染物类型的信息。这些信息对环境监管机构非常有用，可以用来帮助追踪污染物的来源，并帮助制定策略，在这些化学物质损害鱼类和其他动物之前将它们从水中去除。这项研究项目的目的是开发和应用一种新技术（称为“代谢组学”），通过测量鱼类血液和组织中的大量小分子（称为代谢物）来评估鱼类的健康状况。这些测量非常详细，它们可以提供有关鱼类生殖系统的哪些部分（或“代谢途径”）受损的确切信息。这种方法现在也被成功地用于医院评估人类疾病，我们将用它来寻找野生鱼类的独特模式或“特征”，以确定它们是否受到损害，如果受到损害，则由河流中的哪种污染物造成。为了实现这一目标，我们首先需要在实验室中将鱼（蟑螂，我们已经证明蟑螂存在广泛的性破坏）暴露于被怀疑与野生鱼类繁殖中断有关的单一污染物中，并测量每种化学物质造成的损害。这些实验将包括对鱼进行短时间和长时间的曝光，其中一些将持续两年，以准确模拟真实的环境情景。然后，我们将“训练”计算机识别污染物引起的损害的特定模式，这些计算机将在野生鱼类中搜索这些模式，就像它们可以通过基因指纹搜索与犯罪现场收集的指纹相匹配一样。“代谢组学”的另一个优点是，与大多数现有的环境监测方法不同，它可以快速进行，只需从鱼身上提取一分钟的血液，然后将其释放回河中。最后一个好处是，对血液中某些代谢物的测量，特别是那些被称为“性类固醇”的代谢物，可以告诉我们很多关于鱼的生殖健康的信息，也就是说，这些分子测量与整条鱼的整体健康之间存在密切的关系。“代谢组学”中使用的工具通常与化学实验室有关，包括核磁共振波谱学和质谱学。此外，由于将产生大量的数据，也将需要数学专家。我们的多学科团队拥有化学、生物学、毒理学和数学方面的专业知识，并汇集了来自伯明翰大学和埃克塞特大学、环境署、一家水务公司和一家质谱公司的科学家。最终，这项研究的结果将有助于为最终用户开发一种更合适的方法和实用的工具（称为“生物标志物”），这可以有助于环境影响评估和监管当局对排放的监管。这将使我们更加了解河流的健康状况，从而保护我们的水生资源和生物多样性。