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

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 PPARĪ³ ligands that inhibit the expression of PPARĪ³ 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. / Thesis / Master of Science (MSc) / There is concern that chemicals from oil sands mining in the Athabasca oil sands region are hurting the reproductive health of animals in the wild. Some of these animals, including bears, wolves, and river otters, need a bone in their penis called a baculum to reproduce. Studies have shown that some chemicals, including those from mining activity can make the baculum bone weaker. For bone to stay strong, bone cells always need to be developing to fix the bone tissue. The goal of our study was to find how chemicals from mining activity can affect the development of bone cells. We found that a group of chemicals that come from oil sands mining called naphthenic acid fraction components (NAFCs) stop bone cells from developing and making new bone. We also know that having more fat cells in bone is associated with weaker bones. We also looked at whether NAFCs could increase the development of fat cells. However, NAFCs did not increase the development of fat cells. Together, this research shows that NAFCs can make bones like the baculum weaker by slowing the development of new bone, but not by increasing fat cells. Our research suggests that exposure to NAFCs may make baculums weaker which may be bad for the reproductive health of animals living near oil sands mining activity.

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/27437
Date January 2022
CreatorsGutgesell, Robert Michael
ContributorsHolloway, Alison, Medical Sciences (Division of Physiology/Pharmacology)
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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