Sex specific neurodegenerative effects of Endocrine disrupting chemicals

Our aim is to identify environmental contaminants (especially Endocrine Disrupting Chemicals EDCs), their potential neurodegenerative effects, and their pathways via an exposome/metabolome approach. Our transdisciplinary consortium addresses EDC effects within a One Health Framework. We combine in situ, in ovo and in vitro studies to answer raising concern of emerging EDCs in our chemosphere with special focus on their sex specific impact on neurological systems. 

Key Words:
Environmental contaminants, Neurodegeneration, Endocrine disrupting chemicals, EDC
Current research activities:

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. 

 Our consortium answers the call of environmental risks assessment associated with EDCs contamination at the EU scale in the framework of the “zero pollution” ambition of the European Green deal.


The postdoc will be working between the department of Biology (Dr. Céline Arzel, project Disrupt) and Turku Metabolomic Centre (Dr. Alex Dickens).  Secondment might be carried out at the Environmental Endocrine Disruptors Lab at Aarhus University, Denmark with Assoc. Prof. Martin Hansen; at the Norwegian University of Science and Technology – NTNU (Assoc. Prof. Veerle Jaspers); and with other collaborators of our consortium.

This transdisciplinary group is especially suitable for a highly motivated computational biologist. While data on waterbirds is already partly available for bioinformatic analyses, the postdoctoral fellow working with us will have opportunities to carry out different lab work depending on own interests and expertise:
Dr. Céline Arzel
Academy Research Fellow
Docent in Wildlife Research and Management
Associate Editor of Ornis Fennica
Systems medicine and Neurometabolomics groups

Systems medicine combines both systems biology and computational modelling to bring together physiological, genetic, environmental, molecular and biochemical interactions to advance the field of medicine. We focus on metabolomics applications in biomedical research and related integrative bioinformatics. We are particularly interested in the identification of vulnerabilities to disease associated with metabolic phenotypes and the underlying mechanisms linking these vulnerabilities to the development of specific disorders and their co-morbidities. Such in-depth understanding of metabolic phenotypes in health and disease is crucial to enable the development of personalised medicine. In Turku we have access to world leading instrumentation for a wide range of metabolomics based experiments including mass spectrometry based imaging on the state-of-the-art MALDI 2 tims-TOF QTOF instrument and one of the most sensitive triple quad mass spectrometers to enable us to detect metabolites from a single cell. 

Key Words:
Systems medicine, Integrative bioinformatics, Metabolomics, Neurometabolomics, Exposomics, Mass spectrometry, Imaging, Single cell analysis
The current ongoing projects are:
Key Research Infrastructure:

The Turku Metabolomics Centre (TMC) is the leading core facility for metabolomics in Finland and houses state-of-the-art instruments for metabolomics. The main focus is on mass spectrometry but we also have the capacity to perform both solution and solid/semi solid high resolution NMR measurements. The Turku Metabolomics Centre is a joint venture between six laboratories from Åbo Akademi and the University of Turku, with a primary focus on clinical applications of metabolomics. The Centre brings the constituent laboratories under one organisational structure to jointly provide expertise across a variety of complimentary aspects of metabolomics. 

The main focus of the core facility are: 

The constituent laboratories are: 

The core facility has recently purchased the MALDI-2 timsTOF QTof (Bruker) instrument. This allows us to perform imaging mass spectrometry to an eventual resolution of 5 um depending on the molecule. This allows us to map metabolites in tissue allowing the spatial information to be preserved. The full instrumentation list can be found here and a list of what service we offer can be found here. 

Key Research Infrastructure:

The PI of the Systems Medicine Group, Prof Matej Orešič holds a PhD in biophysics from Cornell University. He is a professor in medicine with a specialization in systems medicine at Örebro University and group leader in systems medicine at the Turku Centre for Biotechnology, University of Turku. Prof. Orešič’s main research areas include exposomics and metabolomics applications in biomedical research and systems medicine. He is particularly interested in the identification of environmental exposures (exposome) and disease processes associated with different metabolic phenotypes and the underlying mechanisms linking these processes with the development of specific disorders or their co-morbidities. Prof. Orešič has also initiated the popular MZmine open source project, leading to popular software for metabolomics data processing. 

The PI of the neurometabolomics group, Dr Alex Dickens is a Finnish Academy Fellow and the leader of the Neurometabolomics group at Turku Bioscience Centre, University of Turku. He is also the head of the Turku Centre for Chemical and Molecular Analytics (CCMA), Department of Chemistry and the Co-PI and founder of the Turku Metabolomics Centre with Matej Orešič. He obtained his DPhil from the University of Oxford in 2013 where he utilized NMR based metabolomics to prognose different brain diseases from blood. He then completed two post-doctoral research positions. First in the Turku PET Centre, where he was investigating new tracers for neuroinflammation. Secondly, he went to Johns Hopkins School of Medicine where he identified a new mechanism of how the brain communicates to the periphery via extra cellular vesicles. He also established new MS based lipidomic methods. He then joined the Orešič group in Turku. His current research group focuses on developing new MS based methods for the detection of a wide range of metabolites and then applying these to see metabolism changes following brain injury or development. It particularly focuses on how the endocannabinoid system can act as long range signaling molecules between the brain and periphery. 

Selected publications:
Alex Dickens
Academy Research Fellow
Matej Oresic
Senior Research Fellow
Studies on sedentary behavior, physical (in)activity and exercise at the Turku PET Centre

Cardiometabolic and brain health effects of physical (in)activity are also actively studied at the University of Turku. These studies are conducted, but not limited to studies at the Turku PET Centre by Academy Research Fellow Ilkka Heinonen research group. Our primary general research interest is to elucidate acute and long-term cardiovascular and metabolic adaptations of physical activity and exercise in health and disease. Novel aspects in this area are pursued by studying a broad range of human activity levels, ranging from total inactivity at the epidemiological scale to extreme activities of highly training and performing endurance athletes. These studies are complemented by investigating physiological responses of environmental challenges. 

Recent studies of the research group have included conducting a large 6-month RCT in metabolic syndrome patients investigating cardiometabolic health of reduced daily sitting. This study includes investigations of fitness and accelometer-measured physical activity and essentially glucose metabolism/insulin sensitivity in basically all human organs, such as skeletal muscle, liver, adipose tissue, bone and bone marrow and heart as well as brain. Our group is also currently investigating the effects of acute exercise on brain blood circulation and lymphatic system in healthy volunteers. We have also previously worked with cohort studies led in Turku and are willing to think multidisciplinary studies trying to address cardiometabolic and brain health in a wide range of experimental settings. Further, one of our main research areas currently is (cancer) patient studies including cardiac studies as a way to advance the field of clinical exercise physiology for the health benefits of the patients. 

Key words:
PET imaging, Physical (in)activity, Glucose metabolism, Insulin sensitivity, Cardiometabolism, Brain health
Dr. Ilkka Heinonen
Academy Research Fellow, Turku PET Centre; Docent, Department of Clinical Medicine
Sleep apnea caused multiorgan functional changes: unraveling the mechanisms by PET imaging

Human beings need to sleep for one-third of their lifetime, and the quality of sleep determines the quality of life and socioeconomics at large. Sleep apnea is characterized by breathing pauses during sleep, resulting in intermittent hypoxemia and sleep fragmentation. Sleep apnea affects one billion people in the world. Population-based studies have shown clear links between sleep apnea and other diseases. According to a European sleep apnea cohort study, cardiovascular and metabolic diseases are highly prevalent. In addition, patients with sleep apnea have a higher risk of developing dementia. In sleep apnea, oxygen delivery to tissues and organs is interrupted, which causes intermittent hypoxia and inflammation. As oxygen delivery affects all organs simultaneously, patients with sleep apnea are often multimorbid. This has recently been confirmed by a Finnish nationwide study, which is the largest investigation on multimorbidity in people with sleep apnea in this field. It is, thus, obvious that sleep apnea is a major public health problem affecting the general population. 

    Our research uses positron emission tomography (PET) techniques to study the disease mechanism underlying sleep apnea-induced multiorgan functional changes, with a focus on vascular inflammation and metabolic changes in heart and brain. We use disease models in mice to mimic intermittent hypoxia and sleep fragmentation, and longitudinal PET imaging will be performed to monitor the progression of vascular inflammation and changes in metabolism. Several radiopharmaceuticals are used to visualize different biological and pathological processes. In addition, a clinical study will be carried out in 30 patients with sleep apnea with or without hypoxia (15 patients each group). 

    Sleep research in Finland is active. Finland is the top two contributor regarding the number of sleep research publications per million population, according to a statistics made in year 2023. 

Key words:
Sleep apnea, Vascular inflammation, Heart metabolism, Brain metabolism, Positron emission tomography, PET, Longitudinal PET imaging, In vivo models, Clinical study
Xiang-Guo Li
Assistant Professor
Turku PET Centre, University of Turku
Tarja Saaresranta
Co-PI, Professor
Sleep Research Centre, University of Turku and Turku University Hospital
Metabolic regulation of lipid homeostasis: Protection of whole-body adiposity by inhibiting HSD17B12

HSD17B12 is an enzyme Short-chain dehydrogenases/reductase-family that is known to catalyze hydride and proton transfer by applying nicotinamide as the cofactor. Such activities are involved e.g. in the detoxification of xenobiotics, regulation of signaling molecules such as lipids, steroids and sensing of the redox status in the cells, thus, regulating vital cellular processes. In our previous studies we have shown that inducing HSD17B12 gene disruption at adult age results to a rapid body weight and adipose tissue loss in miceWe have shown that the weight loss observe was not primarily due to an increased metabolic rate of the HSD17B12cKO mice. Neither was there a difference in the locomotor activity. However, the mice drastically reduced water and food consumption after knockout induction. Interestingly, the expression levels of the genes mediating the satiety and hunger signals in the hypothalamus revealed that the major hunger-inducing signaling components were active, pointing towards a novel appetite signaling mechanism. Altogether, the data from human GWAS studies and the data on the mouse models support our hypothesis with the presence of key role of HSD17B12 in the regulation of weight gain, we, thus, propose that inhibiting the enzymatic activity of HSD17B12 could be utilized as novel compound to control whole body adiposityOur hypothesis, supported by preliminary data, is that the deficiency in HSD17B12 results to a defect in the lipid droplet fusion and composition, and the formation of exocytotic granules. We propose that lipid droplet function/exosome composition regulated by HSD17B12 activity is essential to bring the whole body energy sensing. The working hypothesis is challenged by various gene modified mice with several obesity inducing insults, and these studies are complemented with studies on the protein structure, aiming at developing an HSD17B12 tool box inhibitor to be validated in the mouse models.   

Key words:
Weight regulation, Energy sensing, White adipose tissue, WAT, Lipid droplet composition, HSD17B12 enzyme
Selected publications:
Matti Poutanen, Ph.D.
Professor of Physiology
Director, Turku Center for Disease Modeling
Institute of Biomedicine
Research Centre for Integrative Physiology and Pharmacology
Human brown adipose tissue (hBAT) – an important mediator of cardiometabolic health

Brown adipose tissue in the human body is found in several locations but the most prominent site is in supraclavicular region and around neck arteries. hBAT exists in adult humans, not only in newborns and in childhood, and cold exposure and acclimation is one of the tools to keep hBAT active and functional. BAT is thermogenic tissue, and it is possible that heat production in the supraclavicular and neck region has importance for maintaining proper blood temperature circulating to brain.  

We have previously studied physiological function of hBAT by utilizing state-of-the-art method, positron emission tomography (PET) for the visualization hBAT functional activity: oxygen consumption, tissue perfusion, glucose uptake and fatty acid uptake, as well as hBAT adenosine and cannabinoid receptors. People with high hBAT activity have better glycemic control and lipid profile. However, hBAT function appears to subside in obesity, but the recent findings support the importance of active hBAT: people with active hBAT have less cardiometabolic diseases than people with non-active hBAT, regardless of obesity.    

Different ways of activating hBAT are under our current interest. We utilize cold acclimation, food consumption and different pharmacological agents for the activation and thereby aim to understand the overall role of hBAT in brain and cardiometabolic health.  

Key words:
Brown adipose tissue, hBAT, Positron emission tomography, PET, Cardiometabolism, Brain health
Selected publications:
Kirsi Virtanen
Associate Professor, Turku PET Centre
Scroll to Top