Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia

Abstract

Preeclampsia is a hypertensive disease that complicates many pregnancies, typically presenting with new-onset or worsening hypertension and proteinuria. It is well recognized that the placental syncytium plays a key role in the pathogenesis of preeclampsia. This review summarizes the findings pertaining to the structural alterations in the syncytium of preeclamptic placentas and analyzes their pathological implications for the development of preeclampsia. Changes in the trophoblastic lineage, including those in the proliferation of cytotrophoblasts, the formation of syncytiotrophoblast through cell fusion, cell apoptosis and syncytial deportation, are discussed in the context of preeclampsia. Extensive correlations are made between functional deficiencies and the alterations on the levels of gross anatomy, tissue histology, cellular events, ultrastructure, molecular pathways, and gene expression. Attention is given to the significance of dynamic changes in the syncytial turnover in preeclamptic placentas. Specifically, experimental evidences for the complex and obligatory role of syncytin-1 in cell fusion, cell-cycle regulation at the G1/S transition, and apoptosis through AIF-mediated pathway, are discussed in detail in the context of syncytium homeostasis. Finally, the recent observations on the aberrant fibrin deposition in the trophoblastic layer and the trophoblast immature phenotype in preeclamptic placentas and their potential pathogenic impact are also reviewed.

Placenta Of Late Onset Preeclampsia Without Fetal Growth Restriction : Is It Different From The Normal?

“…Increased perivillous fibrin deposition can be due to increased activity of plasminogen activator inhibitor type 1. Some of the PE related complications may be explained by defective exchange of nutrients and gas at fetal maternal interface due to excessive deposition of fibrin [5] .…”

“…Such antiangiogenic substances (serum CD105) and inflammatory cytokines released into the maternal circulation can lead to systemic inflammatory response and endothelial dysfunction [5,6] .…”

The profile analysis of circular RNAs in human placenta of preeclampsia

“…In recent years, more and more studies indicated that the abnormal recasting of spiral arteries and the defect of trophoblast cell invasion play an important role in the pathogenesis of PE. 27,41 In order to explore whether circRNA_3286 affects the invasion of trophoblast cells, Transwell assay was conducted in HTR8/SVneo cells. We found that transfected with si-circ-3286 significantly inhibited the cell invasion capability.…”

Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia

“…Preeclampsia, a life-threatening obstetrical syndrome related to placental dysfunction [32,[57][58][59][60][61][62][63][64][65], is associated with dysregulated expression or function of many PPE proteins (e.g., CGB, LEP), transcription factors (e.g., GCM1, ESRRG), and signaling and kinase pathways (e.g., ERK1/2, p38), especially when it develops preterm [19,57,[66][67][68][69][70][71][72][73][74][75]. Based on the observations that the volume [76] and cellular architecture [67][68][69][77][78][79] of villous trophoblasts are severely impacted in preterm preeclampsia, it has been proposed that either the entire cytotrophoblast differentiation program [80], or particularly syncytialization [81][82][83][84][85][86][87], are affected in preterm preeclampsia, although neither have been proven at the systems level yet. Thus, it would be imperative to explore the dynamic transcriptomic changes during normal cytotrophoblast differentiation to understand its dysregulation in preterm preeclampsia.…”