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Title: Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

Abstract

A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.

Authors:
 [1];  [1]; ORCiD logo [1]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1349079
Report Number(s):
PNNL-SA-123563
Journal ID: ISSN 0143-4004; PII: S0143400417302175
Grant/Contract Number:
AC0576Rl01830; R01 ES022190; R21 HD084788; AC05-76RL01830
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Placenta (Eastbourne)
Additional Journal Information:
Journal Name: Placenta (Eastbourne); Journal Volume: 60; Journal Issue: S1; Journal ID: ISSN 0143-4004
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; deep placentation; pregnancy complications; mass spectrometry imaging; metabolome; lipidome; ion mobility spectrometry- mass spectrometry; Nano-DESI

Citation Formats

Burnum-Johnson, Kristin E., Baker, Erin S., and Metz, Thomas O. Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging. United States: N. p., 2017. Web. doi:10.1016/j.placenta.2017.03.016.
Burnum-Johnson, Kristin E., Baker, Erin S., & Metz, Thomas O. Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging. United States. doi:10.1016/j.placenta.2017.03.016.
Burnum-Johnson, Kristin E., Baker, Erin S., and Metz, Thomas O. Wed . "Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging". United States. doi:10.1016/j.placenta.2017.03.016. https://www.osti.gov/servlets/purl/1349079.
@article{osti_1349079,
title = {Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging},
author = {Burnum-Johnson, Kristin E. and Baker, Erin S. and Metz, Thomas O.},
abstractNote = {A successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Furthermore, problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. Here, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.},
doi = {10.1016/j.placenta.2017.03.016},
journal = {Placenta (Eastbourne)},
number = S1,
volume = 60,
place = {United States},
year = {Wed Mar 29 00:00:00 EDT 2017},
month = {Wed Mar 29 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
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  • Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy relatedmore » problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.« less
  • Cited by 2
  • Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Liquid chromatography and mass spectrometry (LC-MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging duemore » to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are unresolvable using present LC-MS approaches. Here we show that combining structurally-based ion mobility spectrometry (IMS) with LC-MS measurements distinguishes lipid isomers and allows insight into biological and disease processes.« less
  • One of the most significant challenges in contemporary lipidomics lies in the separation and identification of lipid isomers that differ only in site(s) of unsaturation or geometric configuration of the carbon-carbon double bonds. While analytical separation techniques including ion mobility spectrometry (IMS) and liquid chromatography (LC) can separate isomeric lipids under appropriate conditions, conventional tandem mass spectrometry cannot provide unequivocal identification. To address this challenge, we have implemented ozone-induced dissociation (OzID) in-line with LC, IMS and high resolution mass spectrometry. Modification of an IMS- capable quadrupole time-of-flight mass spectrometer was undertaken to allow the introduction of ozone into the high-pressuremore » trapping ion funnel region preceding the IMS cell. This enabled the novel LC-OzID-IMS-MS configuration where ozonolysis of ionized lipids occurred rapidly (10 ms) without prior mass-selection. LC-elution time alignment combined with accurate mass and arrival time extraction of ozonolysis products facilitated correlation of precursor and product ions without mass-selection (and associated reductions in duty cycle). Unsaturated lipids across 11 classes were examined using this workflow in both positive and negative ion modalities and in all cases the positions of carbon-carbon double bonds were unequivocally assigned based on predictable OzID transitions. Under these conditions geometric isomers exhibited different IMS arrival time distributions and distinct OzID product ion ratios providing a means for discrimination of cis/trans double bonds in complex lipids. The combination of OzID with multidimensional separations shows significant promise for facile profiling of unsaturation patterns within complex lipidomes.« less
  • We report on the implementation of a traveling wave (TW) based compression ratio ion mobility programming (CRIMP) approach within Structures for Lossless Ion Manipulations (SLIM) that enables both greatly enlarged trapped ion charge capacities and also their subsequent efficient compression for use in ion mobility (IM) separations. Ion accumulation is conducted in a long serpentine path TW SLIM region after which CRIMP allows the large ion populations to be ‘squeezed’. The compression process occurs at an interface between two SLIM regions, one operating conventionally and the second having an intermittently pausing or ‘stuttering’ TW, allowing the contents of multiple binsmore » of ions from the first region to be merged into a single bin in the second region. In this initial work stationary voltages in the second region were used to block ions from exiting the first (trapping) region, and the resumption of TWs in the second region allows ions to exit, and the population to also be compressed if CRIMP is applied. In our initial evaluation we show that the number of charges trapped for a 40 s accumulation period was ~5×109, more than two orders of magnitude greater than the previously reported charge capacity using an ion funnel trap. We also show that over 1×109 ions can be accumulated with high efficiency in the present device, and that the extent of subsequent compression is only limited by the space charge capacity of the trapping region. Lower compression ratios allow increased IM peak heights without significant loss of signal, while excessively large compression ratios can lead to ion losses and other artifacts. Importantly, we show that extended ion accumulation in conjunction with CRIMP and multiple passes provides the basis for a highly desirable combination of ultra-high sensitivity and ultra-high resolution IM separations using SLIM.« less