Prenatal exposure to bisphenol A up-regulates immune responses, including T helper 1 and T helper 2 responses, in mice.
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.
Yoshino
Shin
S
Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan. yoshino@kobepharma-u.ac.jp
Yamaki
Kouya
K
Li
Xiaojuan
X
Sai
Tao
T
Yanagisawa
Rie
R
Takano
Hirohisa
H
Taneda
Shinji
S
Hayashi
Hideyuki
H
Mori
Yoki
Y
D000818:Animals; D001559:Benzhydryl Compounds; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013268:Stimulation, Chemical; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014874:Water Pollutants, Chemical / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D017252:CD3 Complex; D016207:Cytokines; D004968:Estrogens, Non-Steroidal; D007074:Immunoglobulin G; D007371:Interferon-gamma; D015847:Interleukin-4; D010636:Phenols; D014874:Water Pollutants, Chemical; C006780:bisphenol A; D000098826:Bisphenol A Compounds