IMPACT OF PETROLEUM RELATED COMPOUNDS ON MESENCHYMAL STEM CELL DERIVED PROGENITOR CELLS

Abstract

There is concern over the impact that petroleum related compounds (PRCs) associated with mining activity in the Athabasca Oil Sands Region (AOSR) are having on local wildlife. With the increase in oil sands mining activity in the AOSR there has been a corresponding decline in the fertility of indicator species in the AOSR. One of the primary sources of PRCs in the environment is oil sands process affected water (OSPW), which is stored in tailings ponds. Several PRCs, including naphthenic acid fraction components (NAFC), have endocrine disrupting effects, which may, in part, explain reduced fertility in indicator species. For example, male North American river otters (Lontra canadensis) living in areas impacted by mining activity have lower baculum strength those unaffected by mining activity. Weaker baculums are associated with increases in fracture rates and reduced fertility. Baculum strength is maintained throughout life by bone remodeling, a process that requires the differentiation of osteoblasts. NAFCs can impact several pathways integral to the development and path selection of mesenchymal stem cells into osteoblasts or adipocytes. Therefore, the objective of this thesis was to test the hypothesis that NAFCs inhibit osteoblast differentiation and induce adipocyte differentiation from progenitor cells. We exposed osteoblast progenitor cells and adipocyte progenitor cells to NAFCs. We demonstrated that NAFCs inhibit osteoblast differentiation and activate the glucocorticoid receptor pathway. We also found that NAFCs do not induce adipogenesis in adipocyte precursor cells. Lastly, we showed that NAFCs are PPARγ ligands that inhibit the expression of PPARγ associated genes. These insights into the effects of NAFCs on osteoblast and adipocyte progenitor cells suggest NAFCs may contribute to lower baculum strength and impaired adipose tissue function of animals living in the AOSR. These effects my reduce the fertility and population of wildlife in the AOSR.