The role of autophagy in pregnancy

Abstract

Autophagy is an evolutionarily conserved process in eukaryotes, by which cytoplasmic cargo sequestered inside double-membrane vesicles are delivered to the lysosome for degradation. 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 takes part in the invasion and vascular remodeling in EVTs. On the other hand, soluble endoglin, which increased in sera in preeclamptic cases, suppressed EVT-invasion or -vascular remodeling by inhibiting autophagy in vitro. In addition, a substance selectively degraded by autophagy, p62/SQSTM1, accumulated in EVT cells in preeclamptic placental bed biopsy samples showing impaired autophagy in vivo. There is, however, still a conflict in state of autophagy in preeclamptic placentas. In this paper, we review the importance of autophagy inhibition for placentation, and propose the future direction of autophagy in placenta.