Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells in mice offspring

Environ Toxicol Pharmacol. 2016 Oct;47:149-158. doi: 10.1016/j.etap.2016.09.017. Epub 2016 Sep 26.


Increasing evidence demonstrates that perinatal exposure to Bisphenol A (BPA) can cause immune disorders throughout the life span. However, the biological basis for these immune disorders is poorly understood and the effects of exposure to BPA on Th17 development are unknown. The present study sought to characterize alterations of Th17 cells in childhood and adulthood following gestational and lactational exposure to environmentally relevant low-dose of BPA and the underlying mechanisms. Pregnant dams were exposed to BPA (10, 100 or 1000nM) via drinking water from gestational day (GD) 0 to postnatal day (PND) 21. At PNDs 21 and 42, offspring mice were anesthetized, blood was obtained for cytokine assay and spleens were collected for Th17 cell frequency and RORγt mRNA expression analysis. Perinatal exposure to low-dose BPA resulted in a dose-dependent and gender-specific persistent rise in Th17 cells accompanied by an increase of RORγt mRNA expression in the offsprings. The contents of major Th17 cell-derived cytokines (IL-17 and IL-21) and those essential for Th17 cell differentiation (IL-6 and IL-23) were also increased compared to those in controls. These changes were more pronounced in female than in male offsprings. However, perinatal exposure to low-dose BPA had little effect on serum TGF-β, another key regulator for Th17 cell development. Our results suggest that gestational and lactational exposure to a low-dose of BPA can affect Th17 cell development via an action on its transcription factor and the regulatory cytokines. These findings provide novel insight into sustained immune disorders by BPA exposure during development.

Keywords: Bisphenol A; Cytokine; Maternal exposure; RORγt; Th17 cells.

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity*
  • Birth Weight / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Interleukin-17 / metabolism
  • Interleukin-23 / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Lactation
  • Male
  • Maternal Exposure / adverse effects
  • Mice, Inbred ICR
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Spleen / drug effects
  • Spleen / pathology
  • Th17 Cells / drug effects*
  • Th17 Cells / metabolism
  • Weaning


  • Benzhydryl Compounds
  • Interleukin-17
  • Interleukin-23
  • Interleukin-6
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Phenols
  • interleukin-21
  • bisphenol A