title: Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice.
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 10mg/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 beta-cells. 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 LPS- and 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.
authors.affiliation: * Department of Food, Water and Cosmetics, Norwegian Institute of Public Health, Oslo, Norway;
authors.forename: Johanna
authors.initials: J
authors.lastname: Bodin
authors.forename: Anette Kocbach
authors.initials: AK
authors.lastname: Bølling
authors.forename: Rune
authors.initials: R
authors.lastname: Becher
authors.forename: Frieke
authors.initials: F
authors.lastname: Kuper
authors.forename: Martinus
authors.initials: M
authors.lastname: Løvik
authors.forename: Unni Cecilie
authors.initials: UC
authors.lastname: Nygaard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D001786:Blood Glucose / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D052244:Endocrine Disruptors / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D016688:Mice, Inbred NOD; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D013154:Spleen / Q000254:growth & development / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D016207:Cytokines; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: NOD mice; bisphenol A; developmental toxicity; diabetes mellitus type 1; immunotoxicity; insulitis