{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:35:19Z","timestamp":1779204919975,"version":"3.51.4"},"reference-count":18,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Excess platelet activation by extracellular vesicles (EVs) results in trophoblast inflammasome activation, interleukin 1\u03b2 (IL-1\u03b2) activation, preeclampsia (PE), and partial embryonic lethality. Embryonic thrombomodulin (TM) deficiency, which causes embryonic lethality hallmarked by impaired trophoblast proliferation, has been linked with maternal platelet activation. We hypothesized that placental TM loss, platelet activation, and embryonic lethality are mechanistically linked to trophoblast inflammasome activation. Here, we uncover unidirectional interaction of placental inflammasome activation and reduced placental TM expression: although inflammasome inhibition did not rescue TM-null embryos from lethality, the inflammasome-dependent cytokine IL-1\u03b2 reduced trophoblast TM expression and impaired pregnancy outcome. EVs, known to induce placental inflammasome activation, reduced trophoblast TM expression and proliferation. Trophoblast TM expression correlated negatively with IL-1\u03b2 expression and positively with platelet numbers and trophoblast proliferation in human PE placentae, implying translational relevance. Soluble TM treatment or placental TM restoration ameliorated the EV-induced PE-like phenotype in mice, preventing placental thromboinflammation and embryonic death. The lethality of TM-null embryos is not a consequence of placental NLRP3 inflammasome activation. Conversely, EV-induced placental inflammasome activation reduces placental TM expression, promoting placental and embryonic demise. These data identify a new function of placental TM in PE and suggest that soluble TM limits thromboinflammatory pregnancy complications.<\/jats:p>","DOI":"10.1182\/blood.2020005225","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T12:38:30Z","timestamp":1598963910000},"page":"977-982","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["Placental thromboinflammation impairs embryonic survival by reducing placental thrombomodulin expression"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-7380","authenticated-orcid":false,"given":"Shrey","family":"Kohli","sequence":"first","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital Leipzig, Leipzig University, Leipzig, Germany;"},{"name":"Institute of Clinical Chemistry and Pathobiochemistry, Otto von Guericke University 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