Assessing Maternal-Fetal Exposure Pathways Using Bio-Imaging

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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.