Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
| Autor: | 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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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 18, p 9873 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms22189873 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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