Transmaternal Exposure to Bisphenol A and Phthalates and the Development of Type 1 Diabetes, 2015

The Scandinavian countries have the highest prevalence of type 1 diabetes in the world with a steady increase in Norway of 600 new cases yearly. Type 1 diabetes mellitus (T1DM) is an autoimmune insulin deficiency due to destruction of insulin producing beta-cells. It is the most common type of diabetes in children and is induced by various environmental factors acting on a genetic predisposition. There is a parallel occurrence of increased diabetes prevalence and a high exposure burden of endocrine disruptors (EDs), leaking from consumer products, over the last decades. Continuous presence of these chemicals in urine from adults, children and even infants reflects a constant exposure to EDs. The aim of the project was to investigate the effect of EDs on the development of T1DM. We investigated the effect of combined exposure to some of the most commonly found EDs, bisphenol A, di(2-ethylhexyl) phthalate (DEHP), diisobuthyl phthalate (DIBP), dibuthyl phthalate (DBP) and benzyl buthyl phthalate (BBP), in a mouse model for T1DM. Non obese diabetic (NOD) mice spontaneously develop T1DM and we monitored if the selected endocrine disruptors had an impact on the time of onset and incidence of the disease. To enable fetal and early life exposure we exposed pregnant and lactating mice. Progression of T1DM in pups was monitored through measurements of blood glucose, autoantibodies, proinflammatory cytokines and immuno-phenotyping of peripheral lymph nodes. The degree of insulitis in the pancreas and the amount of apoptotic beta cells was evaluated. Furthermore, the mechanisms involved in beta-cell death were investigated ex vivo in pancreatic islets and in a beta cell-line in vitro. The knowledge gained in this project will help to improve toxicological evaluations and health hazard assessment of EDs since there is limited knowledge on immunological effects of transmaternal exposure to a combination of these chemicals.