Placenta proteome analysis from Down syndrome pregnancies for biomarker discovery

Abstract

Down syndrome is one of the most frequent chromosomal disorders, with a prevalence of approximately 1/500 to 1/800, depending on the maternal age distribution of the pregnant population. However, few reliable protein biomarkers have been used in the diagnosis of this disease. Recent progress in quantitative proteomics has offered opportunities to discover biomarkers for tracking the progression and for understanding the molecular mechanisms of Down syndrome. In the present study, placental samples were analyzed by fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In total, 101 proteins have been firmly identified representing 80 unique gene products. These proteins mainly function in cytoskeleton structure and regulation (such as vimentin and Profilin-1). Additionally, our quantitative proteomics approach has identified numerous previously reported Down syndrome markers, such as myelin protein. Here we present several Down syndrome biomarkers including galectin-1, ataxin-3 and sprouty-related EVH1 domain-containing protein 2 (SPRED2), which have not been reported elsewhere and may be associated with the progression and development of the disease. In summary, we report a comprehensive placenta-based proteomics approach for the identification of potential biomarkers for Down syndrome, in which serum amyloid P-component (APCS) and ataxin-3 have been shown to be up-regulated in the maternal peripheral plasma of Down syndrome cases. The potential of utilizing these markers for the prognosis and screening of Down syndrome warrants further investigation.

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

“…Among these, there are genes involved in oxidative phosphorylation (OXPHOS), including all five mitochondrial complex subunits, genes implicated in mitochondrial biogenesis, and more generally in the mitochondrial function. Microarray analyses of DS samples showed a marked downregulation of genes encoding mitochondrial proteins, called nuclear-encoded mitochondrial genes (Conti et al 2007 ; Chen et al 2012 ; Sullivan et al 2016 ; Liu et al 2017 ; Sobol et al 2019 ; Lee et al 2003 ) (Table 2 ).…”

Bayesian GWAS and network analysis revealed new candidate genes for number of teats in pigs

“…ATXN3 shares this biological process with this gene. This gene is also known as Machado-Joseph disease (MJD) and encodes for Ataxin-3 protein which might a play role in neurodegeneration and modulate the aggregation of abnormal peptides in the pathogenesis of the diseases in human (Chen et al 2012). It has been reported to have its expression altered when induced by stradiol, diethylstilbestrol, and octyl-phenol in the uterus of immature rats (Hong et al 2006).…”

Expression of CPPED1 in human trophoblasts is associated with timing of term birth

“…Proteomic analyses of placental blood plasma and cervicovaginal fluids from normal term deliveries have identified proteins linked to immune and defence responses and inflammation and oxidative stress, respectively. Proteomic analyses of placenta have also focused on foetal growth restriction , early pregnancy loss , pre‐eclampsia , down syndrome , differences between first‐ and third‐trimester human placentas and low molecular weight components in the chorionic and basal plates of placenta .…”