PLA2G6 in attenuating ferroptosis

The study found that spontaneous preterm birth (SPTB) is associated with ferroptosis and that inhibition of GPX4 causes ferroptotic injury in primary human trophoblasts and during mouse pregnancy. Importantly, the role for the phospholipase PLA2G6, known to metabolize Hp-PE to lyso-PE and oxidized fatty acid, was uncovered in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia/reoxygenation injury in vivo. Together, ferroptosis signaling and the role for PLA2G6 in attenuating trophoblastic ferroptosis in the human and mouse placenta was identified, which provided mechanistic insights into the ill-defined placental lipotoxicity that may inspire PLA2G6-targeted therapeutic strategies