6.1.1 Abnormal ferroptosis to Hypoxia/Reperfusion during pregnancy
Before 10 weeks into the pregnancy, blood clots and congealed endothelial cells fully block the maternal spiral arteries. The embryo’s environment is hypoxic and hypoglycemia during 8–10 weeks. The spiral arteries don’t fully open until 10 to 12 weeks of pregnancy, when maternal blood can enter the placental gap and initially expose the fetal villi to an environment rich in glucose, oxygen, and iron. Similar to the hypoxia/reperfusion event, which causes excessive cell membrane lipid peroxidation and ferroptosis at the maternal-fetal interface, especially in trophoblast cells, this mechanism causes excessive cell membrane lipid peroxidation. The pathologic characteristics of PE are caused by superficial endovascular invasion of extravillous cytotrophoblast cells and inadequate remodeling of the maternal spiral arteries. Placental ischemia and oxidative stress are caused by inadequately modified spiral arteries, which also cause insufficient placental perfusion, high-speed blood flow, and turbulence,83 thus damaging placental villi and causing abnormal levels of angiogenic proteins in maternal blood.84