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

Arch Toxicol. 2019 Apr;93(4):1083-1093. doi: 10.1007/s00204-019-02419-4. Epub 2019 Mar 2.


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.

Keywords: Bisphenol A; Immunomodulation; Microbiome; NOD mice; Type 1 diabetes; Window of exposure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / immunology
  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity*
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / microbiology
  • Diabetes Mellitus, Type 1 / chemically induced*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / microbiology
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology
  • Gestational Age
  • Male
  • Mice, Inbred NOD
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / microbiology
  • Sex Characteristics*


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • bisphenol A