Formation of the placental membranes and pathophysiological origin of associated great obstetrical syndromes.

Formation of the smooth membranes is an essential phase of human placentation to allow safe rupture of the chorionic sac and birth of the fetus without damaging the placenta. The membranes form through regression of two-thirds of the villi that cover the early gestational sac shortly after implantation. Regression is associated with locally high levels of oxidative stress secondary to partial onset of the maternal arterial circulation to the placenta. Onset starts preferentially in the peripheral zone from ∼6 to 8 weeks of gestation, reflecting the lesser extent of plugging of maternal spiral arteries by endovascular trophoblast in this region. Plugging is part of the arterial remodeling essential to control adequate and even perfusion of the placenta. As the chorionic sac expands, extensive necrosis occurs in the overlying decidua capsularis, which consequently makes no contribution to the mature membranes. Once the sac fuses with the decidua parietalis lining the opposite wall of the uterus, at around 16 weeks of gestation, the cytotrophoblast cells of the chorionic epithelium proliferate and form a stratified epithelium with features reminiscent of the skin barrier. A sharp demarcation exists between this epithelium and the cells of the decidua parietalis in the mature membranes, with no evidence of trophoblast migration. Preterm premature rupture of the membranes and preterm labor are associated with deficient remodeling of the spiral arteries that is mediated by extravillous trophoblasts derived from the cytotrophoblastic shell. The resultant placental malperfusion causes maternal and placental oxidative stress, as in the other great obstetrical syndromes, causing release of proinflammatory cytokines and stimulating uterine contractility. Deficient remodeling is also likely a proxy marker for poor development of the cytotrophoblastic shell. The shell anchors the gestational sac at the maternal-placental interface postimplantation, and weakness of this interface predisposes to subchorionic hemorrhage. Hemorrhages that abut the membranes may induce local inflammation, senescence, and weakening. Ensuring normal development of the cytotrophoblastic shell is therefore essential to prevent the great obstetrical syndromes. At this stage of pregnancy, placental development is supported by histotrophic nutrition from the decidua. Hence, optimizing endometrial function prior to conception should become a healthcare priority.