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Arch Toxicol. 2019 Apr;93(4):997-1008. doi: 10.1007/s00204-018-2379-5. Epub 2019 Jan 2.

Sex-dependent effects of bisphenol A on type 1 diabetes development in non-obese diabetic (NOD) mice.

Author information

1
Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
2
Department of Environmental Health Sciences, University of Georgia, Athens, GA, 30602, USA.
3
Department of Pathology, University of Georgia, Athens, GA, 30602, USA.
4
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, 30602, USA.
5
Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA. tlguo1@uga.edu.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease caused by immune-mediated pancreatic β-cell destruction. The endocrine disrupting chemical bisphenol A (BPA) has widespread human exposure and can modulate immune function and the gut microbiome (GMB), which may contribute to the increasing T1D incidence worldwide. It was hypothesized that BPA had sex-dependent effects on T1D by modulating immune homeostasis and GMB. Adult female and male non-obese diabetic (NOD) mice were orally administered BPA at environmentally relevant doses (30 or 300 µg/kg). Antibiotic-treated adult NOD females were exposed to 0 or 30 µg/kg BPA. BPA accelerated T1D development in females, but delayed males from T1D. Consistently, females had a shift towards pro-inflammation (e.g., increased macrophages and Bacteroidetes), while males had increases in anti-inflammatory immune factors and a decrease in both anti- and pro-inflammatory GMB. Although bacteria altered during sub-acute BPA exposure differed from bacteria altered from chronic BPA exposure in both sexes, the GMB profile was consistently pro-inflammatory in females, while males had a general decrease of both anti- and pro-inflammatory gut microbes. However, treatment of females with the antibiotic vancomycin failed to prevent BPA-induced glucose intolerance, suggesting changes in Gram-positive bacteria were not a primary mechanism. In conclusion, BPA exposure was found to have sex dimorphic effects on T1D with detrimental effects in females, and immunomodulation was identified as the primary mechanism.

KEYWORDS:

Bisphenol A; Immunomodulation; Microbiome; NOD mice; Type 1 diabetes; Vancomycin

PMID:
30600366
PMCID:
PMC6511313
[Available on 2020-04-01]
DOI:
10.1007/s00204-018-2379-5

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