Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia

Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive.

We used placentae from normotensive and preeclampsia pregnancy cohorts, human H9 embryonic stem cells differentiated into cytotrophoblast-like cells, and placenta-specific Phd2 −/− preeclamptic mice. Lipid peroxidation and iron cargo of placenta-derived small extracellular vesicles (sEVs) isolated from the maternal circulation of control and preeclampsia individuals were examined by mass spectrometry, flow cytometry, and colorimetry. Human microvascular endothelial cells’ angiogenic capacity and function were examined after exposure to control and pathological sEVs.