Figure 1.

Two-stage theory of the pathogenesis of PE. The pathogenesis of PE is explained by the two-stage theory: in the first stage, EVTs as the paternally antigenic fetal components infiltrate toward the spiral artery without being eliminated by the maternal immune system due to immune tolerance by Treg and other immune cells, and supply a large amount of maternally derived blood to the placenta resulted in the successful placentation. However, when placentation is impaired by the breakdown of immune tolerance, anti-angiogenic factors and proinflammatory factors produced by placental ischemia in the second stage are released into the systemic circulation, causing multiple organ failure due to the vascular injury. Treg: regulatory T cell; dNK: decidual natural killer cell; Th: helper T cell; sFlt-1: soluble fms-like tyrosine kinase-1; sEng: soluble endoglin; TNF-α: tumor necrosis factor-α; INF-γ: interferon-γ; eCT: endovascular cytotrophoblast.