The traditional scientific method involves setting up a hypothesis (proposed explanation), using this hypothesis to derive predictions that can be tested in experiments, and then determining whether the experimental observations agree or conflict with this hypothesis. In ERGO, we use this approach to look at the hormone system and study biological processes that are known to be influenced by hormones. For instance, we look at swim bladder inflation or eye development in zebrafish, study the microscopic anatomy of hormone-producing glands and measure hormone concentrations in blood and tissue. In this way, we gradually increase our knowledge and get closer to breaking down the wall between human health and environmental testing of endocrine disruptors.
There is, however, one limitation to the traditional scientific method: we only find what we are looking for. This raises the question of how do we expand our view on how endocrine disrupting chemicals affect organisms? How can we know that we are looking at the most relevant effects? Could there be other biochemical pathways that are important to study? Could we instead try to interrogate the whole biological system and let the organism’s response guide our investigations? This is why ERGO, in addition to traditional hypothesis driven research, also applies non-targeted methods such as metabolomics.
Metabolomics is the comprehensive study of small molecules present in cells, tissues, biofluids or whole organisms. The set of these molecules in a given biological medium is called the metabolome. ERGO partner, Aarhus University (AU), uses state-of-the-art mass spectrometry-based technologies to conduct metabolomics investigations. Together with fellow ERGO partners, École Normale Supérieure de Lyon (ENSL) and Ruprecht-Karls-Universität Heidelberg (UHEI), they have recently conducted studies on the effects of the model chemical, propylthiouracil (PTU) on the metabolome of mice and zebrafish. PTU is a pharmaceutical drug used to treat excessive production of thyroid hormones. It is therefore expected to affect the circulating levels of thyroid hormones. Initial results of the non-target metabolomics analysis showed that, in addition to having an effect on thyroid hormone levels, other biochemical pathways such as fatty acid biosynthesis are also affected in both animal species. This gives new ideas for further investigations of how chemicals can have wide-ranging disruptive effects and how we can contribute to the overall aim of ERGO, breaking down the wall between human health and environmental testing of endocrine disruptors.
For more information on this research, please contact Rikke Poulsen (firstname.lastname@example.org)