Autophagy in Preeclampsia

Abstract

Autophagy is an evolutionarily conserved process in eukaryotes by which cytoplasmic cargo sequestered inside double-membrane vesicles is delivered to the lysosome for degradation. Recently, there is increasing evidence that modulating autophagy accumulates during pregnancy. In early pregnancy, trophoblasts and the fetus experience hypoxic and low-nutrient conditions; nevertheless, extravillous trophoblasts (EVTs) invade the uterine myometrium up to one third of its depth and migrate along the lumina of spiral arterioles, replacing the maternal endothelial lining. An enhancement of autophagy induced by physiological hypoxia occurs during the invasion and vascular remodeling in EVTs. However, soluble endoglin, which is increased in sera in preeclamptic cases, suppresses EVT invasion or vascular remodeling by inhibiting autophagy in vivo. In addition, a substance selectively degraded by autophagy, p62/SQSTM1, accumulates in EVT cells in preeclamptic placental biopsy samples showing impaired autophagy in vivo. On the other hand, there are some reports about autophagy activation in preeclamptic placentas. Though changes in autophagy may affect the fates of mothers and babies, controversy remains for the evaluation of autophagy status in preeclampsia. In this chapter, we will introduce the role of autophagy in embryogenesis, implantation, and maintaining pregnancy and discuss the autophagy status in preeclampsia.