A mouse model for investigating the environmental obesogen effects of Perfluoroalkyl substances (PFASs) and Mercury (Hg)

The aim of the main project is to study the effects of PFASs and Hg in modulating lipid homeostasis leading to obesogenic and estrogenic effects with general physiological and health implications of the exposed organisms, using small rodents as model organisms in field experiments. Our hypothesis is that exposure of rodents to environmental levels of PFASs and Hg from hotspot areas (related to skiing activities and ski wax) will produce changes in biological processes that regulate lipid homeostasis and endocrine toxicity in wild rodents. We will study the occurrence and toxicological effects (lipid, oxidative stress and endocrine) of PFASs and Hg in free ranging rodents from hotspot areas around Granåsen, Trondheim, and use a reference site near Jonsvatnet, Trondheim as control. The general health and physical parameters (weight, length and pathology) will be recorded. We will record the density of the rodents of interest in different stations in the wild (%-age caught in cage traps). A maximum of 240 animals will be sacrificed by cervical dislocation under anesthesia and analyzed for blood and tissue levels of PFASs and Hg. The cage traps are designed to prevent unnecessary stress, and the anesthesia will prevent pain and distress during blood sampling from the heart and during the euthanizing. We will analyze muscle and liver membrane lipid compositions, and isolate peripheral lymphocytes from blood for genotoxicity analysis and perform PPARs, estrogen receptors (ERs) and oxidative stress responses at gene, protein and enzyme levels. Relationships between all the above named parameters will be evaluated using principal component analysis (PCA) and other modeling methods. These data will provide significant insight into the general health effects of PFAS and Hg in the environment.