The Repository @ St. Cloud State

Open Access Knowledge and Scholarship

Date of Award


Culminating Project Type


Degree Name

Biological Sciences - Cell and Molecular: M.S.




College of Science and Engineering

First Advisor

Marina Cetkovic-Cvrlje

Second Advisor

Maureen Tubbiola

Third Advisor

Nathan Winter

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Keywords and Subject Headings

Type 1 diabetes, Bisphenol A, T-cells, Th-1 immune response, Cytokines, Streptozotocin


Type 1 diabetes (T1D) has been historically, and continues to be the most common type of diabetes in children and adolescents, affecting nearly three million people in the Unites States. It is an autoimmune disorder characterized by the deficiency of insulin due to the T-cell-mediated autoimmune destruction of insulin-producing pancreatic beta cells. Strong advances have been made associating genetics to the development of T1D, however, an increase of disease incidence cannot be explained by genetic factors only, focusing attention to environmental triggers. Bisphenol A (BPA) is an endocrinedisruptive environmental pollutant, found in plastic products, toys, and inner lining of can products. It is believed that BPA exposure is associated with adverse health effects in humans, such as obesity, type 2 diabetes, reproductive disturbances, and autoimmune diseases. However, the association of BPA and T1D has not been extensively scrutinized. The goal of this study was to investigate the effects of BPA on T1D development and its mechanism of action in the context of T-cells in a multiple low-dose streptozotocin (MLDSTZ)-induced T1D mouse model. It was hypothesized that BPA treatment of mice would increase diabetes incidence and potentiate the severity of disease through its alteration of T-cell populations and their function. To test this, four-weeks-old male C57BL/6 mice were exposed to 1 and 10 mg/L BPA dissolved in drinking water up to 16 weeks of age. To initiate the development of T1D, mice received five intraperitoneal injections of 40 mg/kg STZ at nine weeks of age. Glucose measurements were taken twice a week throughout the experiment. At the end of experimental period, on day 50 post first STZ injection, pancreata were analyzed for severity of mononuclear cell infiltration (insulitis). In addition, on day 11 and 50 post the first STZ injection, spleens were harvested and analyzed for composition, proliferation, and cytokine profiles of T-cells. In summary, the study showed that long-term exposure of MLDSTZ-treated C57BL/6J mice to low, as well as high BPA dose, potentiated diabetes development and insulitis severity. Whereas both BPA doses exhibited immunomodulatory activities, their diabetogenic mechanism of action appeared to be divergent. Thus, low-dose BPA exposure initiated diabetogenesis through the alteration of T-cell populations and skewing their function towards a proinflammatory Th1-like immune response early on during disease development, whereas high-dose BPA treatment did not show these effects. Overall, these results confirmed diabetogenic potential of BPA and its immunomodulatory effects on the T-cells, bringing awareness of BPA as a potential environmental trigger for the development of human T1D.


First and foremost, I would like to express my deepest gratitude to my mentor and research advisor, Dr. Marina Cetkovic-Cvrlje from Biology department, for being a constant source of knowledge, inspiration, and encouragement throughout this research. Not only did she give me an invaluable opportunity to join her research team as an undergraduate student and work my way up to being her graduate thesis student, she also provided academic advice and moral support throughout my time at St. Cloud State University. I am tremendously thankful for her faith in me, giving me a chance to work with her as the immunology research team lead, and countless conversations from which I learned more than I can put in words. Additionally, I am indebted to the remainder of my committee: Dr. Maureen Tubbiola and Dr. Nathan Winter, whose insightful comments helped me improve my research, and to Brian Lorenz, the vivarium manager for his assistance throughout my Master’s program. I would like to convey my sincere gratitude to the Office of Sponsors Program for funding my project and giving me the wonderful opportunity to present at the annual research colloquium. I am also endlessly appreciative of alumni graduate assistants, Jordan Kuiper, Marin Olson, Cordelia Dunai, and talented undergraduate research students, not only for teaching me and constantly giving me suggestions, but also for their never-ending support and guidance over the past few years. Finally, I would like to express my deepest appreciation for my parents, siblings, and friends for being a continual source of moral support. Their faith and love, brought me success throughout my college career.



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