Postnatal Complications of Perinatal Polychlorinated Biphenyl Exposure - Project

项目总结(项目2--斯旺森的皮尔逊) 多氯联苯是一种氯化有机污染物，具有高度的脂溶性。 以相对化学稳定性和在环境中普遍存在为特征的毒素。这些特点是 对其作为严重环境公共卫生风险来源的广泛认可的作用负责。多氯联苯 已经被证明可以穿过胎盘进入母乳，最近的一篇论文表明，产前 有机氯水平有助于儿童特定性别肥胖的发展。在老鼠模型中， 进一步的观察显示，后代在围产期接触到PCB126，这是一种共面的PCB126 通过芳烃受体，与后代相比，它们的脂肪和瘦肉质量明显更差 出生在经过车辆处理的水坝上。此外，暴露于多氯联苯的水坝所生的成熟后代血糖受损。 与车辆处理过的水坝的后代相比，耐受性。首席调查组已经表明， 在健康孕前和哺乳期间进行短期的产妇自愿锻炼可以增强长期的 子代的葡萄糖动态平衡。这项拟议研究的目标是阐明潜在的长期- 多氯联苯在宫内和早期关键期的健康并发症及毒性机制 探讨母体运动作为一种跨代干预的产后生活。具体目标1将确立 围产期接触多氯联苯的时间(未暴露/宫内暴露/出生后暴露/出生后暴露)的重要性 子宫+出生后暴露)，导致后代糖耐量受损。子代的一部分将 喂食高脂肪饮食，以确定“二次打击”是否会加剧多氯联苯引起的损害。特定的 目的2阐明暴露于多氯联苯水坝的子代糖耐量受损的机制。 具体目标3将测试自愿的母体锻炼是否可以作为保护成年后代的干预措施 来自围产期多氯联苯暴露的长期影响。拟议中的研究将提供新的病因学 支持当前观察结果的证据表明，围产期接触环境中的多氯联苯很重要 美国糖尿病流行的贡献者。这项工作也将为创新做出新的贡献 理解运动在减轻多氯联苯暴露对环境健康影响中的作用的见解 通过强调怀孕是环境污染物可能会产生重大和长期影响的敏感期- 对后代新陈代谢的持久影响以及干预措施何时被证明在改善 有害的健康后果。预期结果尤其重要，因为它们很早就突显了出来 发育阶段，即胎儿和新生儿，可能特别容易受到艾滋病的持久影响 印刷电路板污染对有毒环境的侮辱。

PROJECT SUMMARY (Project 2 - Pearson, Swanson) Polychlorinated biphenyls (PCBs), one of a number of chlorinated organic pollutants, are highly lipid-soluble toxins that are characterized by relative chemical stability and prevalence in the environment. These traits are responsible for their widely recognized role as a source of serious environmental public health risks. PCBs have been shown to cross the placenta and enter breast milk, and a recent paper suggests that prenatal organochlorine levels contribute to gender-specific obesity development in children. In a mouse model, additional observations revealed that offspring exposed perinatally to PCB 126, a coplanar PCB that acts through the aryl hydrocarbon receptor, had significantly worse fat and lean mass profiles compared to offspring born to vehicle-treated dams. Further, mature offspring born to PCB-exposed dams had impaired glucose tolerance compared to offspring from vehicle-treated dams. The principal investigator's group has shown that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long- term glucose homeostasis in offspring. The goal of the proposed research is to elucidate the potential long- term health complications and mechanisms of PCB toxicity during the critical periods of in utero and early postnatal life and to explore maternal exercise as a transgenerational intervention. Specific Aim 1 will establish the importance of the timing of perinatal PCB exposure (unexposed/in utero exposure/postnatal exposure/in utero + postnatal exposure) that precipitates impaired glucose tolerance in offspring. A subset of offspring will be fed a high fat diet to determine whether a 'second hit' will exacerbate the PCB-induced detriments. Specific Aim 2 will elucidate the mechanism of impaired glucose tolerance in offspring born to PCB-exposed dams. Specific Aim 3 will test if voluntary maternal exercise can be used as an intervention to protect adult offspring from the long-term effects of perinatal PCB exposure. The proposed studies will provide new etiological evidence supporting current observations that perinatal exposures to environmental PCBs are important contributors to the epidemic of diabetes in the United States. This work will also contribute innovative new insights to understanding the role of exercise in mitigating the environmental health impacts of PCB exposure by highlighting pregnancy as a sensitive period when environmental pollutants could have significant and long- lasting effects on offspring metabolism and when interventions could prove effective in ameliorating the detrimental health outcomes. Anticipated results are particularly significant in that they highlight early developmental stages, i.e., fetal and neonatal, as potential periods of particular vulnerability to lasting effects of toxic environmental insult from PCB contamination.