Mst3 Plays an Important Role in Hypoxia‐induced placental Apoptosis in Preeclampsia

Abstract

Preeclampsia, a disorder unique to humans, affects 5‐10% of all pregnancies, and remains a leading cause of fetal and maternal morbidity and mortality. A key histopathologic correlation is shallow invasion and aberrant remodeling of maternal spiral arteries, leading to decreased uteroplacental perfusion and hypoxia. In preeclampic human placenta, hypoxia is thought to be the main cause to elevate oxidative stress and induced trophoblast cell death. Recently, mammalian Ste20‐like protein kinase 3 (Mst3) was found to be elevated in human preeclampic placenta that exhibit extensive sign of apoptosis, suggesting the participation of Mst3 in preeclampsia. Hypoxia is postulated to induce the expression of Mst3 and the apoptosis of human placenta during preeclampsia. The role of Mst3 in hypoxia‐induced apoptosis was demonstrated in both human placental explant culture and the human trophoblast cell line 3A‐sub‐E. Further studies show that, in human trophoblast, hypoxia may induce the expression of Mst3 via oxidative stress and the activation of JNK. The activated Mst3 then triggers apoptosis of human trophoblasts by both caspase‐dependent and independent pathways. (The work was supported by National Science Council, ROC (Taiwan) under Contract No. NSC‐97‐2311‐B‐009‐001‐MY3)