Procoagulant extracellular vesicles alter trophoblast differentiation in mice by a thrombo-inflammatory mechanism

Markmeyer P, Lochmann F, Singh KK, Gupta A, Younis R, Shahzad K, Biemann R, Hübner H, Rübner M, Isermann B, Kohli S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 22

Article Number: 9873

Journal Issue: 18

DOI: 10.3390/ijms22189873

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-me-diated 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 plate-let-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-inflamma-tion on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation.

Authors with CRIS profile

Hanna Hübner Department of Obstetrics and Gynaecology Matthias Rübner Department of Obstetrics and Gynaecology

Involved external institutions

Universitätsklinikum Leipzig DE Germany (DE)

How to cite

APA:

Markmeyer, P., Lochmann, F., Singh, K.K., Gupta, A., Younis, R., Shahzad, K.,... Kohli, S. (2021). Procoagulant extracellular vesicles alter trophoblast differentiation in mice by a thrombo-inflammatory mechanism. International Journal of Molecular Sciences, 22(18). https://doi.org/10.3390/ijms22189873

MLA:

Markmeyer, Paulina, et al. "Procoagulant extracellular vesicles alter trophoblast differentiation in mice by a thrombo-inflammatory mechanism." International Journal of Molecular Sciences 22.18 (2021).

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