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ORIGINAL RESEARCH article

Front. Toxicol.
Sec. Neurotoxicology
Volume 6 - 2024 | doi: 10.3389/ftox.2024.1452974
This article is part of the Research Topic Methods and Protocols in Neurotoxicology vol II View all 4 articles

The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following in utero opioid exposures in mouse fetuses

Provisionally accepted
Dustyn Barnette Dustyn Barnette 1*Amy Inselman Amy Inselman 1Pravin Kaldhone Pravin Kaldhone 2Grace S Lee Grace S Lee 3Kelly Davis Kelly Davis 1Sumit Sarkar Sumit Sarkar 1Pritpal Malhi Pritpal Malhi 1J Edward Fisher J Edward Fisher 4Joseph P Hanig Joseph P Hanig 4Richard D Beger Richard D Beger 1Ellen Jones Ellen Jones 1
  • 1 National Center for Toxicological Research (FDA), Jefferson, United States
  • 2 Center for Biologics Evaluation and Research (FDA), Bethesda, Maryland, United States
  • 3 Elevar Therapeutics, Salt Lake City, Utah, United States
  • 4 Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States

The final, formatted version of the article will be published soon.

    In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a dynamic approach capable of generating 2D ion images to visualize the distribution of an analyte of interest across a tissue section. Given the importance of lipid metabolism and neurotransmitters in the developing central nervous system, this study incorporates MALDI MSI to assess lipid distributions across mouse fetuses following maternal exposure on gestational day (GD) 8 to morphine (400 mg/kg BW) or the NTD positive control valproic acid (VPA) (500 mg/kg BW). Analysis of whole-body mouse fetuses (GD 18), with and without observable NTDs, revealed differential lipid distributions localized mainly in the brain and spinal cord, which included several phosphatidylcholine (PC) species such as PCs 34:1, 34:0, and 36:2. An increase in the distribution of lyso PC 16:0, was also observed more prominently with maternal morphine exposure than VPA exposure. Neurotransmitter distributions across the brain using FMP-10 derivatizing agent were also assessed, revealing morphine-specific changes. These findings support the feasibility of incorporating MALDI MSI to assess non-standard endpoints of opioid exposure during gestation.

    Keywords: Morphine, Exencephaly, opioid, MALDI MSI, Lipids, hypoxia, Toxicology, development

    Received: 21 Jun 2024; Accepted: 07 Nov 2024.

    Copyright: © 2024 Barnette, Inselman, Kaldhone, Lee, Davis, Sarkar, Malhi, Fisher, Hanig, Beger and Jones. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dustyn Barnette, National Center for Toxicological Research (FDA), Jefferson, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.