PGF and ischemia: There is extensive evidence that placental ischemia and hypoxia promote the release of a variety of active growth factors, including pro-angiogenic factors such as VEGF and placental growth factor (PlGF), as well as anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), anti-inflammatory cytokines TNF-α as reactive oxygen radicals(ROS), IL-6, and HIF (18, 95).