Annexin V inhibits phosphatidylserine-induced intrauterine growth restriction in mice.

To investigate the role of phosphatidylserine (PS) derived from the activated platelets in placental circulation, we established an artificial PS-induced intrauterine growth restriction (IUGR) model in mice and examined whether annexin V, a PS-binding anticoagulant protein, could prevent the development of IUGR in the animal experiments. The ICR mice were injected in the tail vein on days 8, 11 and 14 of pregnancy with filtered PS/phosphatidylcholine (PC) microvesicles (<0.3 microm in maximal diameter). The microvesicles have a procoagulant activity which was inhibited by annexin V in a dose-dependent fashion. The mice were killed on day 18 of pregnancy and the placental and fetal weights were measured. The placental tissue specimens were examined microscopically. PS/PC vesicles induced significant reductions in fetal weights compared with PC vesicles alone. The placental tissue revealed severe congestion with fibrin depositions although the lung and kidney tissue specimens showed minimal histological changes. PS/PC microvesicles with recombinant annexin V showed no significant reductions in fetal weights in mice with PS/PC vesicles alone. These results suggest that PS from the activated platelets induces IUGR by enhancing the coagulation cascade in the placental circulation and that annexin V from the villous trophoblast prevents the development of IUGR.