STOX1

Abstract

See related article, pp 662–668 One of the most vexing and long-lasting conundrums in obstetrics is the underlying cause of preeclampsia. Preeclampsia is a hypertensive disorder of pregnancy, which typically exhibits after the 20th week of gestation, and is characterized by proteinuria, edema, an increased maternal inflammatory response, and widespread maternal vascular dysfunction. Unfortunately, despite intensive research into the pathophysiology of preeclampsia, effective therapeutic interventions for the disorder remain elusive. Currently, the only definitive treatment is parturition and removal of the placenta. It is this last fact which gives a clue to the pathological origins of the disease. Extensive work during the past 20 years on both human subjects and experimental animal models has suggested that a central causative factor in the manifestation of the disorder is placental ischemia, brought about by inadequate remodeling of the maternal spiral arteries that supply the placenta. Under normal circumstances, invasive fetal cytotrophoblasts migrate into the spiral arteries, displacing the endogenous endothelial lining. In the process, they convert the arteries from small high-resistance vessels into distended high-capacity vessels. This process allows for adequate delivery of blood to the developing fetoplacental unit during gestation development. Failure of this process to proceed normally results in chronic hypoxia and ischemia.1 In response, the placental tissue begins producing factors that enter the maternal circulation and are responsible for the symptomatic phase of the disorder, in particular the anti-vascular endothelial growth factor protein soluble fms-like tyrosine kinase 1 (sFlt-1) and the soluble transforming growth factor-β receptor soluble endoglin.2 What remains unclear, however, are the underlying reasons why cytotrophoblast invasion is commonly deficient in preeclamptic placentas. Several mechanisms have been proposed, ranging from maternal immune intolerance to genetic defects in trophoblast signaling. Several recent works have used placental microarray profiling to identify dysregulated genes and genetic screens, including …