Ohshima Yusei, Yamada Akiko, Tokuriki Shuko, Yasutomi Motoko, Omata Nemuko, Mayumi Mitsufumi
Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Shimoaizuki, Matsuoka, Yoshida-gun, Fukui 910-1193, Japan.
Pediatr Res. 2007 Jul;62(1):60-4. doi: 10.1203/PDR.0b013e3180674dae.
Bisphenol A (BPA) is a representative endocrine disruptor that may have adverse effects on human health. Since the development of oral tolerance during infancy may play an important role in the prevention of food allergies, we examined whether transmaternal exposure to BPA influences the development of oral tolerance. To measure antigen-specific responses, female wild-type mice mated with male ovalbumin (OVA)-specific T-cell receptor transgenic (TCR-tg) mice were fed with BPA during pregnancy and while nursing. OVA was administered to OVA-TCR-tg offspring during their weaning period. Oral administration of both high and low doses of OVA suppressed OVA-specific cell proliferation and cytokine production in both BPA-exposed and nonexposed control mice, but the OVA-mediated suppression was significantly more diminished by the BPA exposure. The accumulation of CD4+CD25+Foxp3+ T cells was diminished in the BPA-exposed offspring. Moreover, after low dose OVA administration, serum OVA-specific IgG1 and IgG2a levels were higher in the BPA-exposed offspring than in nonexposed ones. Taken together, our results indicate that transmaternal exposure to BPA seems to modulate the mechanisms underlying tolerance induction; therefore, BPA may partially interrupt the development of oral tolerance.
双酚A（BPA）是一种典型的内分泌干扰物，可能对人类健康产生不利影响。由于婴儿期口服耐受的形成可能在预防食物过敏中起重要作用，我们研究了经母体接触双酚A是否会影响口服耐受的形成。为了测量抗原特异性反应，将与卵清蛋白（OVA）特异性T细胞受体转基因（TCR-tg）雄性小鼠交配的雌性野生型小鼠在怀孕和哺乳期间喂食双酚A。在OVA-TCR-tg后代断奶期间给予OVA。口服高剂量和低剂量的OVA均可抑制双酚A暴露组和未暴露对照组小鼠中OVA特异性细胞增殖和细胞因子产生，但双酚A暴露使OVA介导的抑制作用明显减弱。双酚A暴露的后代中CD4+CD25+Foxp3+T细胞的积累减少。此外，在给予低剂量OVA后，双酚A暴露的后代血清中OVA特异性IgG1和IgG2a水平高于未暴露的后代。综上所述，我们的结果表明，经母体接触双酚A似乎会调节耐受诱导的潜在机制；因此，双酚A可能会部分干扰口服耐受的形成。
