Yoshino Shin, Yamaki Kouya, Li Xiaojuan, Sai Tao, Yanagisawa Rie, Takano Hirohisa, Taneda Shinji, Hayashi Hideyuki, Mori Yoki
Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan.
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.
研究了孕期暴露于双酚A(BPA)对小鼠免疫系统的影响。从与种雄鼠配对当天(第0天)开始,为期18天,每天给未交配的雌性小鼠喂食不同剂量的BPA。在第77天,对其8周龄的雄性后代用鸡卵溶菌酶(HEL)进行免疫。三周后,测量血清中抗HEL免疫球蛋白G(IgG)以及脾细胞对抗原的增殖反应。测量脾淋巴细胞分泌的抗HEL IgG2a和干扰素-γ(IFN-γ)作为辅助性T细胞1(Th1)免疫反应的指标,同时测量抗HEL IgG1和白细胞介素-4(IL-4)作为Th2反应的指标。结果显示,胎儿期暴露于BPA后,抗HEL IgG以及抗原特异性细胞增殖显著增加。孕期暴露于BPA会增强Th1反应(包括抗HEL IgG2a和IFN-γ的产生)和Th2反应(包括抗HEL IgG1和IL-4的产生),尽管Th1反应的增强似乎大于Th2反应。双色流式细胞术分析显示,产前暴露于BPA的小鼠脾脏CD3(+) CD4(+)和CD3(+) CD8(+)细胞分别比对照动物多29%和100%。从孕期摄入BPA的母鼠所生的雌性小鼠中也得到了类似结果。这些结果表明,产前暴露于BPA可能导致成年后免疫反应上调,尤其是Th1反应。