The overarching goal of this study is to address neurodegenerative mechanisms of action of Endocrine Disrupting Chemicals (EDCs) in model organisms and to provide crucial information within Eco and One Health approaches to decision makers. Waterbirds are used to identify and quantify EDCs in our aquatic environment by using untargeted contaminant screening method (exposome/metabolome). Our consortium aims: (i) to characterize the type and quantify the level of the contamination of waterbirds by EDCs, (ii) to assess the biological effects and mechanisms of specific EDCs by in ovo and in vitro experiments with special focus on sex specific neurotoxicity, (iii) to assess the risk of EDCs to humans within the framework of the combined Eco Health and One Health approaches.  

Human and wildlife populations are exposed to EDCs worldwide. EDCs occur in several pollutant classes, e.g. pesticides, per- and polyfluoroalkyl substances, brominated flame retardants, and trace metals/metalloids. They are released in industrial effluents, agricultural runoff or from urban environments, and often transported by air and in waterways. Increasing use of new generations of EDCs has dramatically increased their presence in the environment and is causing growing concern, e.g. in terms of drinking water quality. Waterbirds use and feed in a wide range of aquatic habitats, including marine waters, forest and agricultural wetlands, wastewater treatment basins, drainage canals, ditches and estuaries, exposing them to high risks of contamination by EDCs. Waterbirds provide a number of critical assets for biomonitoring environmental pollution, quantifying global patterns of biodiversity change, providing a warning system as sentinels for the potential impacts on other segments of aquatic ecosystems at local, flyway and global scales and assessing the success of mitigating actions for reducing exposure. For example, many duck species are critical to human health by providing popular game species and by spreading diseases (such as Avian influenza). Increasing egg failure in monitored populations of common Eider Somateria molissima (up to 43% in Finland) and common Goldeneye Bucephala clangula (decline of up to 80% of local breeding population) in the past 5 years, and an increase in the sex ratio bias towards males of several duck species at the global scale, have raised international concerns. In particular neurological symptoms have been reported in ducklings calling for further investigation. Targeted contaminant analyses in breeding female ducks and their eggs on the Finnish breeding ground (project DISRUPT), established the presence of mixture of contaminants of emerging concern (PFASs, phthalates, benzophenones, etc.). Untargeted screening data on Common Eider are available for bioinformatic analyses to complement our understanding of EDCs to which they have been exposed.  

We will utilise a range of animal models (especially ducks and mice) to study neurodegenerative and inflammatory driven disease and to investigate how EDCs of emerging concern found in waterbirds (e.g. PFAS) can impact the brain immune system. Using in ovo exposure experiments, we can directly manipulate exposure during early development of ducklings, providing crucial and novel information on toxicity of emerging EDCs during the vulnerable early life stages. As fundamental hormone signaling appears similar between all vertebrates, our results provide indication of potential risk to mammals and humans. Importantly, the avian embryo is an enclosed self-sufficient system, which can be studied with direct exposure to known levels of contaminants. This is not possible in humans or mammals, and thus birds are an advantageous model for understanding developmental consequences of contaminant exposure. 

The animals exposure to EDCs will be quantified using both untargeted and targeted assays developed in the Turku Metabolomic Centre. The distribution and metabolism changes will be determined with the state of the art mass spectrometry imaging instrument. This allows us to visualize regio-specfic metabolite and lipid changes and correlate this to targeted protein changes. Immunophenotyping will be characterized with Hyperion imaging to understand the changes in the innate and adaptive immune system. Spatial transcriptomics will also be used to understand the underlying changes in the cells following EDC administration.