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

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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.