Altered proteome profiles in maternal plasma in pregnancies with fetal growth restriction

Abstract

Fetal growth restriction (FGR) affects 3-5% of pregnancies and is associated with increased perinatal morbidity and mortality. Currently, there is no reliable biochemical test to differentiate a pathological FGR from a nonpathological one. The objective of this study was to screen whole maternal plasma to identify differentially expressed relatively abundant proteins associated with FGR. We analyzed maternal plasma from FGR (n = 28) and healthy (n = 22) pregnancies using two-dimensional gel electrophoresis (2D-GE) followed by software image analysis. Three spots with molecular weight (M r) 18 kDa corresponding to haptoglobin (hp) α2, as identified by LC-MS/MS and immunoblotting, showed differential expression patterns in FGR. The distribution of hp α2 variants in maternal plasma samples showed the hp α2 variant 1 was low in 72% of FGR, medium in 16%, whereas high in 12%. In comparison, hp α2 variant 1 was high in (41%) of controls, medium in 41%, and low in 18% of cases. Based on the software image analysis, the mean spot volume for hp α2 variant 1 was 0.12 (SD = 0.18) for FGR compared to 0.26 (SD = 0.19) for control (p = 0.006). Given that hp turnover is indicative of its maturation process and is traceable in plasma by its dominant/ suppressed variants, we propose that hp α2 is an important potential target for evaluation of its clinical and pathophysiological role and as a diagnostic biomarker in FGR.

Functional and Complementary Phosphorylation State Attributes of Human Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) Isoforms Resolved by Free Flow Electrophoresis

“…Other samples used in this study involved AF from FGR pregnancies and gestational age-matched controls (n ϭ 6 each) for which consent was obtained from the donors at the time of delivery as described previously (25). All AF samples were collected applying a protease inhibitor mixture.…”

Quantitative 2-D gel electrophoresis-based expression proteomics of albumin and IgG immunodepleted plasma

“…A single blood sample was taken with informed consent and approval as described previously [3]. Electrophoretic equipment and reagents were from Bio-Rad (Hercules, CA, USA) and all procedures were according to manufacturer's instructions unless otherwise specified.…”

“…1-D gels were transferred to PVDF membrane for Western blotting as described previously [3]. Blocking was with 0.5% gelatin for albumin or 2% polyvinyl pyrrolidone (PVP) for IgG.…”

“…Consequently, these proteins are highly relevant both in diagnosis and in therapeutics [1,2]. Our specific interest is in analyzing maternal plasma by 2-D gel electrophoresis (2-DGE) to uncover potential markers of fetal growth restriction [3]. However, proteomic analysis of plasma is challenging due to the plasma proteome's large dynamic range and the presence of highly abundant proteins, such as albumin and IgG [2].…”

Proteomic studies in pregnant and lactating cows. A review

“…Proteomic techniques were used, for instance, in analysis and diagnosis of disturbances in pregnant women and their foetuses. In humans, biomarkers have now been identified for: pre-eclampsia (Blumenstein et al, 2009;Gharesi-Fard et al, 2010), preterm parturition (Horgan et al, 2009), intra-amniotic infection (Gravett et al, 2004), ectopic pregnancy (Gerton et al, 2004), preterm rupture of membranes (Michel et al, 2006) and foetal growth restriction (Gupta et al, 2006).…”