TNF and endothelial dysfunction: It is generally believed that shallow trophoblast invasion and impaired uterine spiral artery remodeling during placentation results in decreased UtBF to the placenta; ischemia/hypoxia further stimulates placenta production of harmful factors such as inflammatory cytokines [i.e., tumor necrosis factor α (TNFα) and interleukin 6 (IL-6)] and antiangiogenic factors (i.e., soluble fms-like tyrosine kinase (sFlt-1), and soluble endoglin), which further cause systemic inflammation and endothelial dysfunction [398,399].