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