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 plateletdependent
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90125 |
| Date | 26 February 2024 |
| Creators | Markmeyer, Paulina, Lochmann, Franziska, Singh, Kunal Kumar, Gupta, Anubhuti, Younis, Ruaa, Shahzad, Khurrum, Biemann, Ronald, Huebner, Hanna, Ruebner, Matthias, Isermann, Berend, Kohli, Shrey |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 9873, 10.3390/ijms22189873 |
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