丝氨酸缺乏通过SP1-BNIP3线粒体自噬途径介导子痫前期代谢重编程机制

Abstract

Preeclampsia (PE) is a devastating hypertensive disorder affecting pregnant women worldwide. Disrupted metabolic reprogramming is recognized as a key feature of placental dysfunction in PE, yet the abnormal metabolic adaption and underlying mechanisms remain largely unknown. In this study, we perform targeted metabolomic profiling and identify placental serine deficiency as a hallmark metabolic alteration in PE, which favors PE occurrence. Serine-deficient chow exacerbates PE-like symptoms, such as hypertension and proteinuria, in mice. Mechanistically, serine deficiency attenuates SAM-dependent methylation, decreasing SP1 levels and impairing SP1-BNIP3-mediated mitophagy, thereby exacerbating oxidative stress to cause placental dysfunction. Notably, targeting serine to the placenta using mPEG 5k -poly(D/L-serine) effectively relieves PE-like symptoms in the mouse model. Our findings elucidate an unknown serine-deficiency-mediated metabolic reprogramming in PE and suggest manipulating serine supplementation as a promising translational strategy for PE treatment.