Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

Abstract

Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered.

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

“…The most consistent being miR-210 which is associated with hypoxia, another process highlighted by the metabolomics studies. Oxidative stress has further been identified as a key process from proteomic studies of preeclampsia (Law, Han, Tong, Baker 2015). Multiple other processes identified in this review including dysregulation of lipids, steroidogenesis, membrane function and energy metabolism have also been reported for a number of different omics.…”

Translational Systems Pharmacology Studies in Pregnant Women

“…As proteins play a pivotal role in understanding the etiology and pathogenesis of PTB and spontaneous preterm deliveries, rich information on the biological mechanisms underlying PTB can be gleaned from proteomic analyses. The majority of the proteomic studies in PTB are based on either changes in the concentration of a protein/peptide or in their differential expression between the preterm and control groups indicating a diagnostic and or predictive factor for PTB . Studies have explored the proteomes of PTB in maternal serum, plasma, fetal and amniotic fluids with or without intra‐amniotic inflammation/infection, and preterm rupture of membranes at an early stage of pregnancy before the onset of symptoms, during the second and third trimesters of pregnancy ( Table ).…”

“…The majority of the proteomic studies in PTB are based on either changes in the concentration of a protein/peptide or in their differential expression between the preterm and control groups indicating a diagnostic and or predictive factor for PTB. 37 Studies have explored the proteomes of PTB in maternal serum, plasma, fetal and amniotic fluids with or without intra-amniotic inflammation/infection, and preterm rupture of membranes at an early stage of pregnancy before the onset of symptoms, during the second and third trimesters of pregnancy (Table 3 38 -45 ). Several highthroughput analytical techniques (e.g., gas chromatographymass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), 1 hydrogen nuclear magnetic resonance ( 1 H-NMR), ultra-performance liquid chromatography (UPLC-MS), immunosorbent assays, iTRAQ matrix-assisted desorption/ionization-mass spectrometry (MALDI-MS)) have been used in proteomic studies to identify as well as measure the biomarkers indiscriminately.…”

Prospective plasma proteome changes in preterm infants with different gestational ages

“…Moreover, time-resolved changes in the plasma proteome composition hold the promise of detecting malfunctioning pathways and highlighting those that are not restored during the early stages of development, possibly contributing to neonatal systemic complications. Indeed, to date, mass spectrometry-based proteomics have been applied in several studies (involving both maternal and fetal plasma specimens) related to pre-eclampsia, 6 necrotizing enterocolitis and lateonset sepsis, 7 markers of the premature rupture of fetal membranes, 8 and the monitoring of the course of parturition. 9 Thus, in the present study, we aimed to systematically compare (by iTRAQ quantitation) plasma proteome compositions in preterm infants at birth and at the 36th week of post-menstrual age in three gestational age-stratified patient subgroups to identify the affected proteins and related signaling pathways that are differentially regulated according to pregnancy duration.…”