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.

Public Health Relevance

The placenta functions to regulate fetal development and the transport of nutrients between the mother and fetus. Our project will fill a significant research gap by determining the environmental impact ofthis critical organ and its utility as a potential biomarker of metal exposure.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZGM1)
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Dartmouth College
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Barr, Fiona D; Ochsenbauer, Christina; Wira, Charles R et al. (2018) Neutrophil extracellular traps prevent HIV infection in the female genital tract. Mucosal Immunol 11:1420-1428
Signes-Pastor, Antonio J; Cottingham, Kathryn L; Carey, Manus et al. (2018) Infants' dietary arsenic exposure during transition to solid food. Sci Rep 8:7114
Salas, Lucas A; Koestler, Devin C; Butler, Rondi A et al. (2018) An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray. Genome Biol 19:64
Deyssenroth, Maya A; Gennings, Chris; Liu, Shelley H et al. (2018) Intrauterine multi-metal exposure is associated with reduced fetal growth through modulation of the placental gene network. Environ Int 120:373-381
Romano, Megan E; Eliot, Melissa N; Zoeller, R Thomas et al. (2018) Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study. Int J Hyg Environ Health 221:623-631
Everson, Todd M; Punshon, Tracy; Jackson, Brian P et al. (2018) Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts. Environ Health Perspect 126:017010
Emond, Jennifer A; Karagas, Margaret R; Baker, Emily R et al. (2018) Better Diet Quality during Pregnancy Is Associated with a Reduced Likelihood of an Infant Born Small for Gestational Age: An Analysis of the Prospective New Hampshire Birth Cohort Study. J Nutr 148:22-30
Nachman, Keeve E; Punshon, Tracy; Rardin, Laurie et al. (2018) Opportunities and Challenges for Dietary Arsenic Intervention. Environ Health Perspect 126:84503
Moen, Erika L; Bynum, Julie P; Austin, Andrea M et al. (2018) Assessing Variation in Implantable Cardioverter Defibrillator Therapy Guideline Adherence With Physician and Hospital Patient-sharing Networks. Med Care 56:350-357
Braun, Joseph M; Chen, Aimin; Hoofnagle, Andrew et al. (2018) Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels. Horm Behav 101:77-84

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