IJzeroverbelasting-geïnduceerde ferroptose veroorzaakt placentadisfunctie bij pre-eclampsie

BACKGROUND:Preeclampsia, a life-threatening hypertensive disorder of pregnancy, has been linked to iron dysregulation, though mechanistic insights remain limited.METHODS:We integrated clinical data, a reduced uterine perfusion pressure mouse model, in vitro trophoblast cell experiments, and placental organoids derived from patients with preeclampsia. Iron metabolism was assessed via mass spectrometry, quantitative polymerase chain reaction, Peris’ Prussian blue staining and immunohistochemistry. Ferroptosis markers and iron transporters were analyzed. Interventions included the iron chelator deferoxamine, antioxidant MitoQ, ferroptosis inhibitor Fer-1 (ferrostatin-1), and the apoptosis inhibitor Z-VAD.RESULTS:Patients with preeclampsia exhibited elevated hemoglobin, ferritin, and serum iron levels from the second trimester, alongside placental iron overload. Single-cell/nucleus RNA sequencing revealed dysregulated iron transporters (TFRC↑,DMT1↑,FPN↓) in preeclampsia trophoblasts. Iron