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While aPLs target the endometrial stroma, little is known about their impact. Endometrial stromal cells (EnSCs) undergo decidualization each menstrual cycle, priming the uterus to receive implanting embryos. Thus, appropriate decidualization and EnSC function is key for establishment of a successful pregnancy. This study was undertaken to explore the effects of aPL on EnSC decidualization, senescence, and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>EnSCs under decidualizing conditions were exposed to aPL or control IgG alone or in the presence of either a Toll\u2010like receptor 4 (TLR\u20104) antagonist, a p38 MAPK inhibitor, a reactive oxygen species (ROS) inhibitor, low molecular weight heparin (LMWH), or acetyl salicylic acid. Secretion of decidualization markers and inflammatory interleukin\u20108 were quantified by enzyme\u2010linked immunosorbent assay, and senescence\u2010associated \u03b2\u2010galactosidase activity was evaluated. In a mouse model of decidualization, aPL or control IgG was administered, and uterine expression levels of decidualization and inflammatory\u2009markers were quantified by real\u2010time quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Antiphospholipid antibodies increased human EnSC decidualization, senescence, and inflammation. This phenotype was recapitulated in the mouse model. The decidualization and inflammatory responses were partially mediated by TLR\u20104 and p38 MAPK, while the decidualization and senescence responses were ROS\u2010dependent. LMWH, commonly used to treat aPL\u2010positive women at risk of obstetric complications, reduced the ability of aPL to increase EnSC decidualization and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings shed new light on the pathogenesis of pregnancy complications in women with aPLs and underscore the benefit of heparin in preventing pregnancy loss in this high\u2010risk population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42068","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T06:34:13Z","timestamp":1642574053000},"page":"1001-1012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Antiphospholipid Antibodies Increase Endometrial Stromal Cell Decidualization, Senescence, and Inflammation via Toll\u2010like Receptor 4, Reactive Oxygen Species, and p38 <scp>MAPK<\/scp> 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