The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood
The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood
复制标题
DOI：
10.1093/toxsci/kfs227
复制
发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Lawrence, B. Paige
中科院分区：
文献类型：
--
作者：
Bauer, Stephen M.;Roy, Anirban;Lawrence, B. Paige
双酚A（BPA）是一种高产量的化学品，被归类为环境雌激素，主要用于塑料工业。BPA使用量的增加与人们体内BPA水平的上升以及哮喘发病率的相应增加有关。由于研究有限，母体BPA暴露对过敏性哮喘发病机制的影响尚不清楚。使用两种已建立的过敏性哮喘小鼠模型，我们研究了发育期暴露于BPA是否会改变成年后代过敏性肺部炎症的标志。从妊娠第6天至产后第21天，对妊娠C57 BL/6母鼠灌胃0、0.5、5、50或500 g BPA/kg/天。为了诱导过敏性炎症，成年后代用含有低剂量脂多糖的卵清蛋白吸入粘膜致敏或用卵清蛋白和明矾ip致敏，然后用卵清蛋白气雾剂激发。在粘膜致敏模型中，与对照组母鼠的后代相比，母体暴露于≥ 50 g BPA/kg/天的雌性后代表现出气道淋巴细胞和肺部炎症增强。与溶剂对照组相比，暴露于50 g BPA/kg/天的腹膜致敏雌性后代出现肺部嗜酸性粒细胞增多。雄性后代在两种致敏模型中均未表现出这些差异。我们的数据表明，母体暴露于BPA对过敏性炎症具有微妙和定性的不同影响，这主要取决于过敏原致敏途径和性别。然而，这些微妙的，但由于发育暴露于BPA的持续变化并没有导致整体气道反应性的显着差异，这表明早期生活暴露于BPA不会加剧过敏性炎症到成年。
Bisphenol A (BPA) is a highproduction volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA's increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 g BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to epsilon 50 g BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to 50 g BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood.