The journey of maternal platelets through the utero-placental circulation: Routes, Interactions and Physiological Implications

Maternal platelets fulfil an exceptional and multifaceted plethora of roles during pregnancy, extending far beyond their traditional function in hemostasis. Increasing evidence suggests that platelets participate in placental development, immune modulation and vascular adaptation at the maternal-fetal interface. This review traces the journey of maternal platelets from a possible adaptation of megakaryopoiesis in the maternal bone marrow to their first encounter with trophoblast cells during early placentation, continuing their way into the intervillous space and eventually leaving the utero-placental circulation returning to maternal peripheral blood. Important hemodynamic changes during pregnancy including a reduction in platelet count and an augmented uterine blood flow will be highlighted. Initial contact of maternal platelets with invading extravillous trophoblasts at the sites of plugging of invaded spiral arteries, are underscored, with further discussion of the influence on trophoblast behavior, vascular remodeling, and local inflammatory signaling. Furthermore, following the routes by which platelets access the intervillous space and interact with the syncytiotrophoblast, the dynamic exchange of soluble mediators, surface receptors and extracellular vesicles is explored. The bidirectional nature of platelet-trophoblast communication is discussed, as are its potential implications for placental function in both physiological and pathological pregnancies. Finally, the possibility is addressed that platelets, following placental interaction, re-enter the maternal vasculature with altered phenotypic or functional properties. This review emphasizes the importance of maternal platelets as active regulators of placental biology and pregnancy outcome by synthesizing current insights.