Placental thromboinflammation impairs embryonic survival by reducing placental thrombomodulin expression

Abstract Excess platelet activation by extracellular vesicles (EVs) results in trophoblast inflammasome activation, interleukin 1? (IL-1?) preeclampsia (PE), and partial embryonic lethality. Embryonic thrombomodulin (TM) deficiency, which causes lethality hallmarked impaired proliferation, has been linked with maternal activation. We hypothesized that placental TM loss, are mechanistically to Here, we uncover unidirectional interaction of reduced expression: although inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine IL-1? expression pregnancy outcome. EVs, known induce proliferation. Trophoblast correlated negatively positively numbers proliferation human PE placentae, implying translational relevance. Soluble treatment or restoration ameliorated EV-induced PE-like phenotype mice, preventing thromboinflammation death. The is a consequence NLRP3 Conversely, reduces expression, promoting demise. These data identify new function suggest soluble limits thromboinflammatory complications.