Assessing Maternal-Fetal Exposure Pathways Using Bio-Imaging

暴露于水和食物中的环境有毒物质会对健康造成威胁，特别是在胎儿期。 这可能会增加儿童在发育和婴儿早期的患病风险，并可能增加以后生活中的疾病风险。胎盘调节婴儿 发展，是一个选择性的障碍，以转移环境污染物之间的母亲 和发育中的胎儿金属可以在胎盘内交叉和积累，这表明 胎盘可以作为暴露的生物标志物。迄今为止，胎盘作为金属生物标志物已被 在流行病学上仅进行了有限的研究。此外，空间分辨金属分析（SRMA， 金属成像）可以揭示金属优先聚集的位置。我们开创了一种新的应用， 空间分辨金属分析作为表征微米和亚微米金属分布的工具 在生物系统中。因此，在拟议的研究中，我们将采用类似的方法来研究金属 在人体胎盘中的分布。这一重要信息将有助于告知胎盘作为一种 流行病学研究中的生物标志物。因此，除了体积平均元素浓度，我们 建议收集胎盘的元素图像，显示一套胎盘的丰度和分布， 化学元素通过激光烧蚀电感耦合等离子体质谱（LA-ICP-MS）从 分娩时收集的胎盘组织是正在进行的新罕布什尔州出生队列研究（NHBCS）的一部分 （n=250）。我们还将充分利用生物标志物的分析和/或收集的优势， NHBCS对母婴配对的影响，并将其与胎盘浓度相关。我们将重点关注砷（As）， 镉（Cd）、汞（Hg）和铅（Pb）作为主要关注污染物，以及锰（Mn） 和钼（Mo），因为最近有证据表明它们在人类健康中的作用。我们还将评估遗传 变异和微量元素共定位，这可能会影响组织和细胞水平的金属分布， 丰饶。特别是，我们将分析脐带血DNA常见的单核苷酸多态性 金属转运蛋白基因的单核苷酸多态性（SNPs）可能是胎盘中As、Cd、Pb和Hg的靶基因， 该信息与人胎盘中的金属积累和/或通过胎盘的转移以及胎儿生物标志物有关。 我们将使用先进的统计方法进行多元素分析和成像统计。这 基础性的工作将使我们能够将胎盘中的金属浓度和分布与 生物反应（例如，基因表达谱）以及临床结果（例如，增长和 发展）在未来。

Exposure to environmental toxicants in water and food can pose health risks, especially during fetal development and early infancy, and may increase disease risk later in life. The placenta regulates infant development and is a selective barrier to the transfer of environmental contaminants between the mother and developing fetus. Metals can both cross and accumulate within the placenta, suggesting that the placenta may be useful as a biomarker of exposure. To date, placenta as a metal biomarker has been examined to only a limited extent epidemiologically. Additionally, spatially resolved metal analysis (SRMA, metal imaging) can reveal where metals preferentially accumulate. We pioneered a novel application of spatially resolved metal analysis as a tool for characterizing metal distribution at the micron and sub-micron level in biological systems. Thus, in the proposed study, we will apply a similar approach to investigate metal distribution in the human placenta. This critical information will help to inform the utility ofthe placenta as a biomarker in epidemiology studies. Therefore, in addition to volume-averaged element concentrations, we propose to collect elemental images of the placenta showing the abundance and distribution of a suite of chemical elements via laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS) from placental tissue collected at delivery as part ofthe ongoing New Hampshire Birth Cohort Study (NHBCS) (n=250). We also will take advantage ofthe full complement of biomarkers analyzed and/or collected in the NHBCS on' mother-infant dyads and relate them placenta concentrations. We will focus on arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) as primary contaminants of interest, as well as manganese (Mn) and molybdenum (Mo) due to recent evidence of their roles in human health. We also will evaluate genetic variation and trace element co-localization, which may influence tissue- and cell-level metal distribution and abundance. In particular, we will analyze cord blood DNA for common single nucleotide polymorphisms (SNPs) in metal transporter genes likely to be the targets of As, Cd, Pb and Hg in the placenta, and to relate this information to metal accumulation in and/or transfer across the human placenta and to fetal biomarkers. We will use advanced statistical approaches for multi-element analysis and imaging statistics. This fundamental work will enable us to relate metal concentrations and distribution in the placenta to markers of biological response (e.g., gene expression profiles) as well as clinical outcomes (e.g., growth and development) in the future.