Maternal platelets were shown to adhere to uteroplacental arteries, which underwent remodeling by invaded fetal trophoblast cells. Moreover, we detected maternal platelets on trophoblast columns of anchoring placental villi and adjacent lining of the intervillous space. Activation of adhering maternal platelets at openings of uteroplacental arteries and anchoring villi represents an underappreciated source of inflammatory chemokines and cytokines at the materno-fetal interface. A localized inflammatory insult or an initial mechanical injury to placental villi have been suggested as initial trigger of perivillous fibrinoid deposition, which has been shown to be increased in some pregnancy pathologies. Accordingly, our preliminary immunohistochemistry analysis showed abundant platelet staining at the villous surface of placental tissue from early-onset PE, compared to age-matched control (DU, KMP). Thus, it is tempting to speculate that platelet-derived factors released from adhering maternal platelets perfuse the intervillous space and thereby contribute to an inflammatory microenvironment in the placenta. An inflammatory intervillous microenvironment is considered to affect villous trophoblast differentiation and function. Our data from trophoblast and placental explant culture showed significantly decreased expression and release of pregnancy hormone human chorionic gonadotropin in response to human platelet lysates, suggesting an adverse effect of platelet-derived factors on placental endocrine activity. On the basis of our preliminary data, the hypothesis will be tested whether or not platelets preferentially adhere to certain trophoblast subtypes and moreover, whether released platelet-derived factors in turn impair hormone secretion from villous trophoblasts. To address this hypothesis, adherence and activation of platelets will be tested on different trophoblast subtypes and cell models using platelet adhesion and degranulation assays (GD). Synthesis and release of placental protein- and steroid hormones in response to platelet-derived factors will be analyzed in trophoblast and placental explant culture from healthy and PE pregnancies (AH). Finally, effects of antiplatelet drug therapy, such as combined aspirin and P2Y inhibitor treatment, will be tested in above mentioned models. Data from this project could open new therapeutic approaches for pregnancy complications related to enhanced placental incidence of adhering maternal platelets and may be the basis for further translational studies.