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

Abstract

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 related 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.

Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution

“…The luminal epithelial (LE) cells lining the uterine cavity are surrounded by stromal (S) cells and dispersed glandular epithelial (GE) cells. These cells show unique cell-type-specific protein expression in preparation for the attachment of early embryos to the LE, and subsequent invasion into the S. Distinct molecular signatures across the heterogeneous landscape of the mouse uterus during early pregnancy has made this an ideal model system for evaluating other imaging techniques such as matrix-assisted laser desorption ionization (MALDI) IMS 30,31 and nanodesorption electrospray ionization (NanoDESI) IMS [32][33][34][35] in previous studies. In this study, our proteomic imaging platform was capable of mapping >2000 proteins with 100-µm spatial resolution, thereby capturing the unique protein expression patterns of the LE, S, and GE cell types.…”

In situ mass spectrometry analysis of intact proteins and protein complexes from biological substrates

“…The various liquid extraction techniques include liquid extraction surface analysis (LESA) [8], nanospray desorption electrospray ionisation (nano-DESI) and devices such as the FlowProbe (Prosolia Inc. Indianapolis, IN) and the MasSpec Pen [9]. In the last decade, these techniques have become established for analysis of small molecules, metabolites and lipids directly from biological samples (LESA [10][11][12], nano-DESI [13][14][15], FlowProbe [16], MasSpec Pen [17]), but in situ protein analysis has proven a greater challenge.…”

Adding a new separation dimension to MS and LC–MS: What is the utility of ion mobility spectrometry?

“…Other recent works focusing on method development for global metabolomics have investigated the use of commercially available TWIMS–MS instrumentation for urine profiling and DTIMS–MS for human plasma and HaCaT cells , whereby improvements in signal‐to‐noise and some confirmed examples of isobar separations have been demonstrated. Other notable recent studies have focused on nontargeted metabolomic assessment of placental samples , and serum profiling . The potential of LC–FAIMS–MS was also explored in a very recent contribution with a broad outlook toward different “omics” approaches .…”