Plasma from first trimester pre-symptomatic women who subsequently developed preeclampsia reduces extravillous trophoblast cells migration, a possible role of placental-derived particles

Abstract

Objectives: The concentration of microparticles is increased in the circulation of women with pre-eclampsia (PE). Failed extravillous trophoblast invasion is associated with early onset of PE. The aim of this study was to quantify the number of particles in plasma from pre-symptomatic women who subsequently developed preeclampsia and establish their effect on EVT migration. Methods: Plasma samples were obtained from normal (NP, n=20) and PE (n=15) pregnancies in the first (11-14 weeks) trimester from Davila Clinic (Santiago, Chile). The number of total particles (TP) and particles with diameter ranging between 30-150 nm (P30-150) were determined using a nanoparticle tracking analysis (NTA, NanoSight NS500). HTR-8/SVneo (EVT) were used as target cells to establish the effect of plasma (10% plasma in RPMI media) from NP and PE pregnancies on migration using a real-time imaging system (Incucyte™). RPMI media was used as control. In addition, plasma was subjected to sonication before exposure to EVT. Results: TP and P30-150 were significantly higher (p<0.05) in plasma from PE compared to normal pregnancies. TP and P30-150 were ∼2.5-fold higher in PE compared to NP. Plasma from NP and PE promote EVT migration (∼3.1-fold and 2.2-fold for NP and PE versus control, respectively). The effect of NP was ∼1.4-fold higher compare to PE (60.3 ± 3.1% and 42.6 ± 3.7% for NP and PE, respectively). In contrast, sonication partially abolished the effect of NP and PE (36.4 ± 1.5% and 33.1 ± 1.4% for NP and PE, respectively), however, the effect of plasma was still higher versus control (19.5 ± 5.0%). Conclusions: Presymptomatic women who subsequently developed PE exhibit a higher number of microvesicles contributing to fail of EVT migration. Early detection of women at risk of complications of pregnancy would provide opportunity to develop and evaluate timely and appropriate intervention strategies to limit acute adverse sequelae.