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Bisphenol A alteration of type 1 diabetes in non-obese diabetic (NOD) female mice is dependent on window of exposure

  • Organ Toxicity and Mechanisms
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Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic β-cell destruction can be mediated by dysbiosis, infiltration of pro-inflammatory immune cells, and cytokines/chemokines. Exposure to bisphenol A (BPA), an endocrine disruptor (ED), can lead to aberrant immunity and gut microbiota. We determined whether BPA had age-dependent effects on T1D by modulating immune homeostasis following various windows of exposure in non-obese diabetic (NOD) mice. Juvenile NOD females were orally exposed to 0 or 30 µg BPA/kg BW from postnatal day (PND) 28 to PND56. Adult NOD females were exposed to 0 or 300 µg BPA/kg BW. Female and male NOD offspring were exposed to 0 or 300 µg BPA/kg BW perinatally from gestation day 5 to PND28 by dosing the dams. It was found that BPA increased T1D risk in juvenile females with gut microbiota shifted towards pro-inflammation (e.g. increased Jeotgalicoccus). In agreement with our previous study, adult females had a trend of increased T1D and a general increase in immune responses. However, female offspring had a reduced T1D development. Consistently, female offspring had a shift towards anti-inflammation (e.g. decreased pro-inflammatory F4/80+Gr1+ cells). In contrast, BPA had minimal effects on immunity and T1D in male offspring. Thus, it was concluded that BPA had age- and sex-dependent effects on T1D with the alteration of gut microbiota and inflammation being the primary mechanisms for T1D exacerbation in juvenile exposure and decreases of inflammation being responsible for attenuated T1D in perinatally exposed females.

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Acknowledgements

We would like to thank Dr. Krzysztof Czaja’s lab for helping measure the male offspring body fat with their Minispec LF110 BAC Analyzer. This study was supported by National Institutes of Health (NIH) R21ES24487, and in part by NIH R41AT009523 and Interdisciplinary Toxicology Program at University of Georgia (UGA).

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Authors and Affiliations

  1. Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602-7382, USA

    Joella Xu & Tai L. Guo

  2. Department of Environmental Health Sciences, University of Georgia, Athens, GA, 30602, USA

    Guannan Huang

  3. Department of Pathology, University of Georgia, Athens, GA, 30602, USA

    Tamas Nagy

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  1. Joella Xu
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  2. Guannan Huang
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Correspondence to Tai L. Guo.

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Xu, J., Huang, G., Nagy, T. et al. Bisphenol A alteration of type 1 diabetes in non-obese diabetic (NOD) female mice is dependent on window of exposure. Arch Toxicol 93, 1083–1093 (2019). https://doi.org/10.1007/s00204-019-02419-4

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