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Analysis of neurotransmitters in rat placenta exposed to flame retardants using IR-MALDESI mass spectrometry imaging

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Abstract

Chemical exposures can adversely impact fetal development. For many compounds, including common flame retardants, the mechanisms by which this occurs remain unclear, but emerging evidence suggests that disruption at the level of the placenta may play a role. Understanding how the placenta might be vulnerable to chemical exposures is challenging due to its complex structure. The primary objective of this study was to develop a method for detecting placental neurotransmitters and related metabolites without chemical derivatization so changes in the abundance and spatial distribution of neurotransmitters in rat placenta following chemical exposure could be determined using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging. Without chemical derivatization, 49 neurotransmitters and their related metabolites were putatively identified in untreated rat placenta sections using mass measurement accuracy and spectral accuracy. A few neurotransmitters were less abundant in placentas that were exposed to various flame retardants and were further investigated by KEGG metabolic pathway analysis. Many of these downregulated neurotransmitters shared the same enzyme responsible for metabolism, aromaticl-amino acid decarboxylase, suggesting a mechanistic role. These data constitute a new approach that could help identify novel mechanisms of toxicity in complex tissues.

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Acknowledgments

The authors would like to thank Dr. Måns Ekelöf for his guidance on the IR-MALDESI instrumentation. All mass spectrometry measurements were carried out in the Molecular Education, Technology, and Research Innovation Center (METRIC) at North Carolina State University.

Funding

This work received financial support from the National Institutes of Health (R01GM087964, R01ES028110, and P30ES025128) and North Carolina State University.

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Authors and Affiliations

  1. FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA

    Crystal L. Pace & David C. Muddiman

  2. Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA

    Brian Horman & Heather Patisaul

  3. Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA

    Heather Patisaul & David C. Muddiman

  4. Molecular Education, Technology and Research Innovation Center (METRIC), North Carolina State University, Raleigh, NC, 27695, USA

    David C. Muddiman

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  1. Crystal L. Pace
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  2. Brian Horman
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  3. Heather Patisaul
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  4. David C. Muddiman
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Corresponding author

Correspondence to David C. Muddiman.

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The authors declare that they have no conflicts of interest.

Use of research animals

This study utilized tissues sourced from animals managed in accordance with the Institute for Laboratory Animal Research Guide. All husbandry practices were approved by North Carolina State University Institutional Animal Care and Use Committee (IACUC).

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Pace, C.L., Horman, B., Patisaul, H. et al. Analysis of neurotransmitters in rat placenta exposed to flame retardants using IR-MALDESI mass spectrometry imaging. Anal Bioanal Chem 412, 3745–3752 (2020). https://doi.org/10.1007/s00216-020-02626-4

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  • DOI: https://doi.org/10.1007/s00216-020-02626-4

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