Related Experiment Videos
Annexin V inhibits phosphatidylserine-induced intrauterine growth restriction in mice
M Sugimura1, T Kobayashi, F Shu
1Department of Obstetrics and Gynecology, Hamamatsu University, School of Medicine, Hamamatsu, Japan. msugi@hama-med.ac.jp
Insights
Activated platelets release phosphatidylserine (PS), a substance that causes intrauterine growth restriction (IUGR) by promoting blood clotting in placental circulation. Annexin V, a PS-binding protein, effectively prevents IUGR development in animal models.
Area of Science:
- Reproductive biology
- Hematology
- Pathology
Background:
- Activated platelets release phosphatidylserine (PS), a procoagulant phospholipid.
- PS exposure in placental circulation is implicated in intrauterine growth restriction (IUGR).
Purpose of the Study:
- To investigate the role of platelet-derived PS in placental circulation and IUGR.
- To determine if annexin V can prevent PS-induced IUGR in a mouse model.
Main Methods:
- An artificial IUGR model was created in ICR mice using PS/phosphatidylcholine (PC) microvesicles.
- Annexin V was administered to assess its inhibitory effect on PS-induced procoagulant activity.
- Fetal and placental weights were measured, and placental tissues were examined microscopically.
Main Results:
- PS/PC microvesicles significantly reduced fetal weights compared to PC vesicles alone.
- Placental tissues showed congestion and fibrin deposition, indicative of coagulation activation.
- Annexin V administration prevented the reduction in fetal weights caused by PS/PC microvesicles.
Conclusions:
- Platelet-derived PS promotes IUGR by activating the coagulation cascade in placental circulation.
- Annexin V, potentially secreted by villous trophoblasts, acts as a protective factor against IUGR.
Abstract:
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.