Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism.
Int J Mol Sci
; 22(18)2021 Sep 13.
Article
in En
| MEDLINE
| ID: mdl-34576036
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Complications, Cardiovascular
/
Extracellular Vesicles
/
NLR Family, Pyrin Domain-Containing 3 Protein
/
Inflammation
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Int J Mol Sci
Year:
2021
Type:
Article
Affiliation country:
Germany