Maternal platelets and extravillous trophoblasts

Recently our published research show that in progressing pregnancy maternal platelets are partially activated at the placental surface during their passage through the placenta, and thereby release their stored platelet factors. The release of these platelet-derived factors seems to have a significant impact on the production of many important pregnancy hormones. Moreover, our new findings reveal that maternal platelets can leave the bloodstream, when entering into the placenta and apparently can leak into intercellular spaces of fetal cells that anchor the placenta to the uterine wall. Subsequent microscopic investigations suggest activation of the maternal platelets in these intercellular spaces. Based on these observations, the influence of platelet activation and the release of platelet-derived factors on fetal placental cells will be investigated in this follow-up project. The effect of the platelet- derived factors on cell differentiation and invasiveness of the placenta cells into the maternal uterine wall will be investigated in detail. These questions have not been investigated before and represent a new scientific concept that opens up novel mechanistic and therapeutic approaches for pregnancy diseases that are associated with increased platelet activation at the placental attachment zone.

For a long time, platelets were primarily regarded as essential components of blood clotting. The results of our project show that during pregnancy they perform many additional functions. They contribute to placental development, help establish the connection between mother and fetus, and regulate developmental, inflammatory, and adaptive processes at the maternal-fetal interface. Platelets continuously communicate with placental cells by releasing signaling molecules and other biologically active factors that influence cellular behavior. Our research focused on early pregnancy, when specialized placental cells invade the lining of the uterus and remodel maternal blood vessels. This process is crucial for ensuring an adequate supply of oxygen and nutrients to the developing fetus. Our findings demonstrate that factors released by maternal platelets directly influence the behavior of placental cells. In particular, they alter the activity of numerous genes involved in developmental processes. One of the most important discoveries was the identification of a molecule called LAIR2, which is produced by specific invasive placental cells during early pregnancy. These cells were predominantly found in areas where the remodeling of maternal blood vessels was especially advanced. Further investigations revealed that LAIR2 suppresses platelet activation while at the same time enhancing the mobility and invasive capacity of placental cells. These findings suggest that LAIR2 helps maintain a balanced interaction between platelets and the placenta. This mechanism may support both the adaptation of maternal blood vessels and the development of a healthy, functional placenta. Overall, the project provides new insights into how maternal platelets contribute to placental development and pregnancy success. By revealing previously unrecognized forms of communication between platelets and placental cells, the research advances our understanding of healthy pregnancy and may help explain complications associated with impaired placental development in the future.