Print Email Facebook Twitter Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice Title Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice Author Bodin, J. Kocbach Bølling, A. Wendt, A. Eliasson, L. Becher, R. Kuper, F. Løvik, M. Nygaard, U.C. Publication year 2015 Abstract Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1. mg/l), a mixture of phthalates (DEHP 1. mg/l, DBP 0.2. mg/l, BBP 10. mg/l and DiBP 20. mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function. © 2015 The Authors. Subject LifeRAPID - Risk Analysis for Products in DevelopmentELSS - Earth, Life and Social SciencesBiomedical InnovationToxicologyHealthy LivingBisphenol ADiabetes mellitus type 1ImmunotoxicityInsulitisNOD micePhthalatesPrenatal exposure4,4' isopropylidenediphenolCaspase 3CD68 antigenGamma interferonGlucoseInsulinInterleukin 10Interleukin 4Interleukin 6Nitric oxidePhthalic acidTestosteroneTranscription factor FOXP3Tumor necrosis factor alphaAnimal cellAnimal experimentAnimal modelAnimal tissueBlood glucose monitoringControlled studyCytokine releaseEnvironmental exposureFlow cytometryHistopathologyImmunocytochemistryImmunohistochemistryIncidenceInsulin dependent diabetes mellitusInsulin releaseLymphocytic infiltrationMaleMousePancreas isletPhagocytosisRegulatory T lymphocyte To reference this document use: http://resolver.tudelft.nl/uuid:03a46809-6aa0-4d35-be9e-a8d9a3759d7a DOI https://doi.org/10.1016/j.toxrep.2015.02.010 TNO identifier 524111 ISSN 2214-7500 Source Toxicology Reports, 2, 99-110 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.