Proteomic analysis of human placental syncytiotrophoblast microvesicles in preeclampsia

Abstract

BackgroundPlacental syncytiotrophoblast microvesicles (STBM) are shed into the maternal circulation during normal pregnancy. STBM circulate in significantly increased amounts in preeclampsia (PE) and are considered to be among contributors to the exaggerated proinflammatory, procoagulant state of PE. However, protein composition of STBM in normal pregnancy and PE remains unknown. We therefore sought to determine the protein components of STBM and whether STBM protein expressions differ in preeclamptic and normal pregnancies.Patients with PE (n = 3) and normal pregnant controls (n = 6) were recruited. STBM were prepared from placental explant culture supernatant. STBM proteins were analyzed by a combination of 1D Gel-LC-MS/MS. Protein expressions levels were quantified using spectral counts and validated by immunohistochemistry.ResultsOver 400 proteins were identified in the STBM samples. Among these, 25 proteins were found to be differentially expressed in preeclampsia compared to healthy pregnant controls, including integrins, annexins and histones.ConclusionSTBM proteins include those that are implicated in immune response, coagulation, oxidative stress, apoptosis as well as lipid metabolism pathways. Differential protein expressions of STBM suggest their pathophysiological relevance in PE.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-0275-11-40) contains supplementary material, which is available to authorized users.

Placental exosomes in normal and complicated pregnancy

“…45 Proteomic and lipidomic contents of microvesicles generated by syncytiotrophoblasts have also been investigated in normal and complicated pregnancies. 28,59 Microvesicles in these reports ranged from 30 nm-1 mm in size. Of the w200 lipids reported, higher levels of phosphatidylserine and lower phosphatidic acid, phosphatidylglycerol, and ganglioside mannoside 3 were reported in pregnancies complicated with preeclampsia and recurrent miscarriage compared to controls.…”

“…59 Proteomic studies identified w400 proteins in the syncytiotrophoblast samples with 25 of these proteins (eg, integrins, annexins, and histones) unique to preeclampsia compared to healthy pregnant controls. 28 Exosomes as potential biomarkers of placental function Previous studies have established that extracellular vesicles, including exosomes, are released under normal physiological and pathophysiological conditions, and it has also been observed that exosome release is negligible in nonpregnant women's circulation compared to healthy normal pregnant women. 23 During gestation the rates of release of these vesicles is increased and this occurs also in response to different pathological conditions 60 presumably due to exosomal secretion from placental trophoblastic cells to the maternal peripheral circulation.…”

“…8,26,28,29 In addition, exosome may contain cell-specific moieties. For example, placental exosomes contain specific miRNAs derived from the chromosome 19 miRNA cluster and placental proteins (eg, PLAP) that are exclusively expressed in the placenta.…”

Noninvasive nucleic acid–based approaches to monitor placental health and predict pregnancy-related complications

“…11 The pathophysiological effect of circulating STBMs is associated with several nonspecific molecules that have proinflammatory and disrupting effects on the maternal endothelium only after being released from the cell (so-called danger molecules, ie, tissue factor, fibronectin, or heat shock protein). 11,20 The shedding of STBMs may be increased in response to hypoxia and reoxygenation stress that is associated with shallow placentation and leads to a cascade of maternal immunological responses that contribute to endothelial damage and maternal hypertension. 21 Necrosis likely coexists with apoptotic processes but occurs more frequently when coupled with a stressful environment.…”

Extracellular presence/release of galectins from HTR-8/SVneo extravillous trophoblast cells*

“…EVs have been associated with most (patho)physiological processes studied so far (Vlassov et al, 2012;Record, 2014). EVs carry different molecular messengers: proteins, RNA (mRNA and microRNA), lipids, and small molecules (Valadi et al, 2007;Baig et al, 2014).…”