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首页> 外文期刊>Environmental Health: A Global Access Science Source >Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study
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Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study

机译：胎儿双酚A暴露是儿童哮喘发展的危险因素：一项动物模型研究

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Background The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility. Methods Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPA-loaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages. Results Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased by day 5 and approached adult levels by day 25. Conclusions Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.
机译：背景技术在工业化国家中，哮喘的患病率急剧上升，现在，哮喘是美国儿童中最常见的慢性疾病。这种增加的迅速性强烈表明，环境暴露的变化是这种流行病的可能原因。此外，变态反应表现的早期发作表明这些暴露可能会影响免疫系统的产前发育。我们已经集中研究了双酚A（BPA）（一种最大的化学污染物）对儿童哮喘的发展的潜在影响。我们已经报道了围产期BPA暴露促进了小鼠模型中过敏性哮喘的发展。当前的研究旨在确定BPA暴露的关键时期，并开始阐明这种敏感性的机制。方法从怀孕前一个星期到研究结束，雌性BALB / c小鼠的饮用水中含10 micro g / ml BPA。在出生后的48小时内，其中一些幼犬从其BPA负载的母亲转移到未暴露的母亲，反之亦然。一半的幼犬用低剂量的实验性过敏原卵清蛋白（OVA）致敏，其余的则以PBS作为未致敏对照。在第22天，通过吸入卵清蛋白或PBS，然后对嗜酸性粒细胞的定量和其气道反应性过高，对幼崽进行攻击，这是该经典小鼠模型中实验性哮喘的主要指标。 UDP-葡糖醛酸糖基转移酶（Ugt）的两个同工型的肝表达通过定量RT-PCR在不同年龄进行定量。结果在子宫内和通过母乳或仅在子宫内接触BPA的幼犬，对它们的“次优”变态反应致敏，表现出哮喘表型，而仅在出生后从母乳中接触BPA的幼犬则没有。 Ugt2b1（一种与大鼠BPA清除相关的同种型）的表达在小鼠胎儿和新生幼崽中未检出，但在第5天增加，到第25天达到成人水平。结论产前暴露会产生与环境相关的BPA负担，其次是产后变态反应的致敏和挑战，促进了实验性变应性哮喘的发展。 BPA代谢酶的延迟表达可能至少部分解释了胎儿对这种常见环境污染物的敏感性增强。

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