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

• 批准号: NE/D002508/1
• 负责人: Mark Viant
• 金额: $ 24.2万
• 依托单位: University of Birmingham
• 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%2FD002508%2F1
• 关键词: Diagnosing; Toxicant; Specific; Disruption; Sexual

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因素是否正在损害生活在我们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污水，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因暴露于污水处理厂废水中所含的化学物质而受到损害，这些化学物质会破坏人体的性激素系统。虽然科学家现在有工具来确定鱼类生殖系统是否受到损害，但这些工具通常涉及杀死鱼类和检查解剖的组织，这对于广泛的影响监测方案来说并不理想。此外，现有的工具没有提供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，可用于帮助追踪污染物的来源，并帮助设计在这些化学品损害鱼类和其他动物之前将其从水中去除的策略。该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大量的小分子（称为代谢物）来评估鱼类的健康状况。这些测量非常详细，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“签名”，以确定它们是否受到损害，如果受到损害，河流中的污染物类型。为了实现这一目标，我们首先需要在实验室中将鱼类（蟑螂，我们已经显示出广泛的性破坏）暴露于被怀疑与野生鱼类生殖中断有关的单一污染物中，并测量这些化学物质造成的损害。这些实验将包括短期和长期的鱼暴露，其中一些将持续两年，以准确地模拟真实的环境场景。然后，我们将“训练”计算机识别污染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，就像它们可以搜索遗传指纹以匹配在犯罪现场收集的指纹一样。“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，只需要从鱼身上取一分钟的血，然后再放回河里。最后一个优点是，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，即，在这些分子测量和整条鱼的整体适合度之间存在密切关系。“代谢组学”中使用的工具通常与化学实验室有关，包括核磁共振光谱和质谱。此外，由于将产生大量的数据，也需要数学专家。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以及环境署，水务公司和质谱公司的科学家。最终，这项研究的结果将有助于为最终用户开发更合适的方法和实用工具（称为“生物标记”），这有助于环境影响评估和监管机构对排放的监管。这将使我们对河流的健康状况有更全面的了解，从而保护我们的水生资源和生物多样性。

项目成果

Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring: hurdles, achievements, and future outlook.

• DOI: 10.1289/ehp.0900985
• 发表时间: 2010-01
• 期刊: Environmental health perspectives
• 影响因子: 10.4
• 作者: Van Aggelen G;Ankley GT;Baldwin WS;Bearden DW;Benson WH;Chipman JK;Collette TW;Craft JA;Denslow ND;Embry MR;Falciani F;George SG;Helbing CC;Hoekstra PF;Iguchi T;Kagami Y;Katsiadaki I;Kille P;Liu L;Lord PG;McIntyre T;O'Neill A;Osachoff H;Perkins EJ;Santos EM;Skirrow RC;Snape JR;Tyler CR;Versteeg D;Viant MR;Volz DC;Williams TD;Yu L
• 通讯作者: Yu L

Distinguishing between the metabolome and xenobiotic exposome in environmental field samples analysed by direct-infusion mass spectrometry based metabolomics and lipidomics.

• DOI: 10.1007/s11306-014-0693-3
• 发表时间: 2014
• 期刊: METABOLOMICS
• 影响因子: 3.6
• 作者: Southam, Andrew D.;Lange, Anke;Al-Salhi, Raghad;Hill, Elizabeth M.;Tyler, Charles R.;Viant, Mark R.
• 通讯作者: Viant, Mark R.

Genomics in Regulatory Ecotoxicology - Applications and Challenges

监管生态毒理学中的基因组学 - 应用和挑战

• DOI: 10.1201/9781420066838.ch3
• 发表时间: 2007
• 作者: Van Leeuwen K

Genomic Approaches for Cross-Species Extrapolation in Toxicology

毒理学中跨物种外推的基因组方法

• DOI: 10.1201/9781420043648.ch1
• 发表时间: 2006
• 作者: Cook J