Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism |
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| Authors: | Paulina Markmeyer Franziska Lochmann Kunal Kumar Singh Anubhuti Gupta Ruaa Younis Khurrum Shahzad Ronald Biemann Hanna Huebner Matthias Ruebner Berend Isermann Shrey Kohli |
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| Affiliation: | 1.Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig University, 04103 Leipzig, Germany; (P.M.); (F.L.); (K.K.S.); (A.G.); (R.Y.); (K.S.); (R.B.);2.Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany;3.Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany; (H.H.); (M.R.) |
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| Abstract: | Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation. |
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| Keywords: | thrombo-inflammation extracellular vesicles inflammasome trophoblast differentiation |
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