Prenatal exposure to bisphenol A up-regulates immune responses, including T helper 1 and T helper 2 responses, in mice

Immunology. 2004 Jul;112(3):489-95. doi: 10.1111/j.1365-2567.2004.01900.x.


The effect of prenatal exposure to bisphenol A (BPA) on the immune system in mice was investigated. Virgin female mice were fed varying doses of BPA, on a daily basis, over a period of 18 days commencing on the day of pairing with stud males (day 0). On day 77, their male offspring of 8 weeks were immunized with hen egg lysozyme (HEL). Three weeks later, anti-HEL immunoglobulin G (IgG) in sera, and proliferative responses of spleen cells to the antigen, were measured. Anti-HEL IgG2a and interferon-gamma (IFN-gamma), secreted from splenic lymphocytes, were measured as indicators of T helper 1 (Th1) immune responses, while anti-HEL IgG1 and interleukin-4 (IL-4) were measured as indicators of Th2 responses. The results showed that fetal exposure to BPA was followed by significant increases in anti-HEL IgG as well as antigen-specific cell proliferation. Both Th1 responses (including anti-HEL IgG2a and IFN-gamma production) and Th2 responses (including anti-HEL IgG1 and IL-4 production) were augmented by prenatal exposure to BPA, although the augmentation of Th1 responses appeared to be greater than that of Th2 responses. Two-colour flow cytometric analysis showed that mice exposed prenatally to BPA had 29% and 100% more splenic CD3(+) CD4(+) and CD3(+) CD8(+) cells, respectively, than control animals. Similar results were obtained from females whose mothers had consumed BPA during pregnancy. These results suggest that prenatal exposure to BPA may result in the up-regulation of immune responses, especially Th1 responses, in adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Division / drug effects
  • Cytokines / immunology
  • Estrogens, Non-Steroidal / pharmacology*
  • Female
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Lymphocyte Count
  • Male
  • Mice
  • Phenols / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Stimulation, Chemical
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Water Pollutants, Chemical / pharmacology*


  • Benzhydryl Compounds
  • CD3 Complex
  • Cytokines
  • Estrogens, Non-Steroidal
  • Immunoglobulin G
  • Phenols
  • Water Pollutants, Chemical
  • Interleukin-4
  • Interferon-gamma
  • bisphenol A