Culminating Project Title
Date of Award
Culminating Project Type
Biological Sciences - Cell and Molecular: M.S.
College of Science and Engineering
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.
Thinamany, Sinduja, "Bisphenol A Potentiates Development of Streptozotocin-Induced Type 1 Diabetes in an Experimental Mouse Model" (2016). Culminating Projects in Biology. 18.