Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia

Abstract

Preeclampsia is the most common placental pathology in pregnant females, with increased morbidity and mortality incurred on the mother and the fetus. There is a need for improved biomarkers for diagnosis and monitoring of this condition. Placental syncytiotrophoblasts at the maternal-fetal interface release nanoparticles, including extracellular microvesicles, into the maternal blood during pregnancy. Syncytiotrophoblast extracellular microvesicles (STEVs) are being studied for their diagnostic potential and for their potential physiologic role in preeclampsia. We hypothesized that STEV profiles in maternal circulation would be altered under conditions of preeclampsia compared to normal pregnancy. Extracellular vesicles (EVs) released by BeWo cells in vitro showed high expression of syncytin-1, but no plac1 expression, demonstrating that trophoblast cell EVs express syncytin-1 on their surface. Placental alkaline phosphatase also showed high expression on BeWo EVs, but due to concern for cross reactivity to highly prevalent isoforms of intestinal and bone alkaline phosphatase, we utilized syncytin-1 as a marker for STEVs. In vivo, syncytin-1 protein expression was confirmed in maternal plasma EVs from Control and Preeclampsia subjects by Western blot, and overall, lower expression was noted in samples from patients with preeclampsia (n = 8). By nanoparticle analysis, EV profiles from Control and Preeclampsia groups showed similar total plasma EV quantities (p = 0.313) and size distribution (p = 0.415), but STEV quantitative signal, marked by syncytin-1 specific EVs, was significantly decreased in the Preeclampsia group (p = 2.8 × 10 −11). Receiver operating characteristic curve demonstrated that STEV signal threshold cutoff of <0.316 was 95.2% sensitive and 95.6% specific for diagnosis of preeclampsia in this cohort (area under curve = 0.975 ± 0.020). In conclusion, we report that the syncytin-1 expressing EV profiles in maternal plasma might serve as a placental tissue specific biomarker for preeclampsia.

Human Placental Trophoblasts Are Resistant to Trypanosoma cruzi Infection in a 3D-Culture Model of the Maternal-Fetal Interface

“…Lastly, and consistent with former reports ( Corry et al, 2017 ; Bayer et al, 2018 ; Levine et al, 2020 ), we observed that 3D-cultured JEG-3 cells released factors that prevented T. cruzi ’s growth in non-trophoblast mammalian cells ( Figure 5 ). It is well documented that secreted type III interferons mediate trophoblast’s protection from Zika virus infection ( Chen et al, 2017 ; Corry et al, 2017 ) and that STs respond to Toxoplasma gondii infection by producing immunomodulatory chemokines that limit parasite growth at the level of attachment and replication ( Ander et al, 2018 ).…”

Association of placenta‐derived extracellular vesicles with pre‐eclampsia and associated hypercoagulability: a clinical observational study

“…These findings are consistent with recent reports that syncytiotrophoblast‐derived EVs contribute to the pathogenesis of PE by EV‐bound metalloprotease neprilysin, 38 which cleaves several peptides that regulate vascular tension, 39 and microRNA‐101, which regulates trophoblast proliferation 40 . A recent report further shows that the while pcEVs express both PLAP and syncytin‐1, levels of syncytin‐1 + pcEVs were significantly reduced in PE patients, as compared to NP women 41 . EVs from endothelial cells, platelets, and erythrocytes were also significantly elevated in PE patients, compared to NP women (Figure 2), potentially amplifying the effects of pcEVs.…”

Syncytiotrophoblast extracellular microvesicles in preeclampsia

“…This short communication is a commentary on Levine and Habertheuer's paper titled, "Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia" published in: Scientific Reports -Nature [1].…”

“…interface release nanoparticles, including extracellular microvesicles (EVs), including exosomes, into the maternal blood during pregnancy [1]. Maternal EVs may provide a window for development of noninvasive biomarker platform in aiding in diagnosis and earlier surveillance of preeclampsia [4][5][6][7][8][9][10][11][12][13][14][15][16].…”