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Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism

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 throm...

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Autores principales: Markmeyer, Paulina, Lochmann, Franziska, Singh, Kunal Kumar, Gupta, Anubhuti, Younis, Ruaa, Shahzad, Khurrum, Biemann, Ronald, Huebner, Hanna, Ruebner, Matthias, Isermann, Berend, Kohli, Shrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466022/
https://www.ncbi.nlm.nih.gov/pubmed/34576036
http://dx.doi.org/10.3390/ijms22189873
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author Markmeyer, Paulina
Lochmann, Franziska
Singh, Kunal Kumar
Gupta, Anubhuti
Younis, Ruaa
Shahzad, Khurrum
Biemann, Ronald
Huebner, Hanna
Ruebner, Matthias
Isermann, Berend
Kohli, Shrey
author_facet Markmeyer, Paulina
Lochmann, Franziska
Singh, Kunal Kumar
Gupta, Anubhuti
Younis, Ruaa
Shahzad, Khurrum
Biemann, Ronald
Huebner, Hanna
Ruebner, Matthias
Isermann, Berend
Kohli, Shrey
author_sort Markmeyer, Paulina
collection PubMed
description 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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spelling pubmed-84660222021-09-27 Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism Markmeyer, Paulina Lochmann, Franziska Singh, Kunal Kumar Gupta, Anubhuti Younis, Ruaa Shahzad, Khurrum Biemann, Ronald Huebner, Hanna Ruebner, Matthias Isermann, Berend Kohli, Shrey Int J Mol Sci Article 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. MDPI 2021-09-13 /pmc/articles/PMC8466022/ /pubmed/34576036 http://dx.doi.org/10.3390/ijms22189873 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Markmeyer, Paulina
Lochmann, Franziska
Singh, Kunal Kumar
Gupta, Anubhuti
Younis, Ruaa
Shahzad, Khurrum
Biemann, Ronald
Huebner, Hanna
Ruebner, Matthias
Isermann, Berend
Kohli, Shrey
Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title_full Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title_fullStr Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title_full_unstemmed Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title_short Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
title_sort procoagulant extracellular vesicles alter trophoblast differentiation in mice by a thrombo-inflammatory mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466022/
https://www.ncbi.nlm.nih.gov/pubmed/34576036
http://dx.doi.org/10.3390/ijms22189873
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