Niedzwiecki Megan M, Austin Christine, Remark Romain, Merad Miriam, Gnjatic Sacha, Estrada-Gutierrez Guadalupe, Espejel-Nuñez Aurora, Borboa-Olivares Hector, Guzman-Huerta Mario, Wright Rosalind J, Wright Robert O, Arora Manish
Exposure Biology, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1057, New York City, New York NY 10029, USA.
Metallomics. 2016 Apr;8(4):444-52. doi: 10.1039/c6mt00010j. Epub 2016 Mar 18.
Fetal exposure to essential and toxic metals can influence life-long health trajectories. The placenta regulates chemical transmission from maternal circulation to the fetus and itself exhibits a complex response to environmental stressors. The placenta can thus be a useful matrix to monitor metal exposures and stress responses in utero, but strategies to explore the biologic effects of metal mixtures in this organ are not well-developed. In this proof-of-concept study, we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to measure the distributions of multiple metals in placental tissue from a low-birth-weight pregnancy, and we developed an approach to identify the components of metal mixtures that colocalized with biological response markers. Our novel workflow, which includes custom-developed software tools and algorithms for spatial outlier identification and background subtraction in multidimensional elemental image stacks, enables rapid image processing and seamless integration of data from elemental imaging and immunohistochemistry. Using quantitative spatial statistics, we identified distinct patterns of metal accumulation at sites of inflammation. Broadly, our multiplexed approach can be used to explore the mechanisms mediating complex metal exposures and biologic responses within placentae and other tissue types. Our LA-ICP-MS image processing workflow can be accessed through our interactive R Shiny application 'shinyImaging', which is available at or through our laboratory's website, .
胎儿暴露于必需金属和有毒金属会影响其一生的健康轨迹。胎盘调节着从母体循环到胎儿的化学物质传递，并且自身对环境应激源表现出复杂的反应。因此，胎盘可以作为监测子宫内金属暴露和应激反应的有用基质，但探索该器官中金属混合物生物学效应的策略尚未得到充分发展。在这项概念验证研究中，我们使用激光烧蚀电感耦合等离子体质谱法（LA-ICP-MS）测量了低体重儿妊娠胎盘组织中多种金属的分布，并开发了一种方法来识别与生物反应标记物共定位的金属混合物成分。我们新颖的工作流程包括为多维元素图像堆栈中的空间异常值识别和背景扣除定制开发的软件工具和算法，能够实现快速图像处理以及元素成像和免疫组织化学数据的无缝整合。使用定量空间统计方法，我们在炎症部位识别出了不同的金属积累模式。总体而言，我们的多重方法可用于探索介导胎盘和其他组织类型内复杂金属暴露和生物反应的机制。我们的LA-ICP-MS图像处理工作流程可通过我们交互式的R Shiny应用程序“shinyImaging”访问，该应用程序可在我们实验室网站或通过该网站获取。
