Title
Transmaternal bisphenol a exposure accelerates diabetes type 1 development in NOD mice
Author
Bodin, J.
Bølling, A.B.
Becher, R.
Kuper, F.
Løvik, M.
Nygaard, U.C.
Publication year
2014
Abstract
Diabetes mellitus type 1 is an autoimmune disease with a genetic predisposition that is triggered by environmental factors during early life. Epidemiological studies show that bisphenol A (BPA), an endocrine disruptor, has been detected in about 90% of all analyzed human urine samples. In this study, BPA was found to increase the severity of insulitis and the incidence of diabetes in female non obese diabetic (NOD) mice offspring after transmaternal exposure through the dams' drinking water (0, 0.1, 1, and 10 mg/l). Both the severity of insulitis in the pancreatic islets at 11 weeks of age and the diabetes prevalence at 20 weeks were significantly increased for female offspring in the highest exposure group compared to the control group. Increased numbers of apoptotic cells, a reduction in tissue resident macrophages and an increase in regulatory T cells were observed in islets prior to insulitis development in transmaternally exposed offspring. The detectable apoptotic cells were identified as mostly glucagon producing alpha-cells but also tissue resident macrophages and betacells. In the local (pancreatic) lymph node neither regulatory T cell nor NKT cell populations were affected by maternal BPA exposure. Maternal BPA exposure may have induced systemic immune changes in offspring, as evidenced by alterations in LPSand ConA-induced cytokine secretion in splenocytes. In conclusion, transmaternal BPA exposure, in utero and through lactation, accelerated the spontaneous diabetes development in NOD mice. This acceleration appeared to be related to early life modulatory effects on the immune system, resulting in adverse effects later in life. © The Author 2013. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Subject
Life
RAPID - Risk Assessment Products in Development
ELSS - Earth, Life and Social Sciences
Food and Nutrition
Biology
Healthy Living
Bisphenol A
Developmental toxicity
Diabetes mellitus type 1
Immunotoxicity
Insulitis
NOD mice
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http://resolver.tudelft.nl/uuid:c019d981-7ea3-4cd2-acf6-b8112f989e4d
DOI
https://doi.org/10.1093/toxsci/kft242
TNO identifier
489146
ISSN
1096-6080
Source
Toxicological Sciences, 137 (2), 311-323
Article number
kft242
Document type
article