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The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor. Cytokine release from monocytes following exposure to lipopolysaccharide (LPS) and the presence of lysine 4\u2010trimethylated histone 3 (H3K4me3) within <jats:italic>TNF<\/jats:italic> promoter sequences were evaluated. Single\u2010cell transcriptomic profiles of circulating monocytes from women with PE or uncomplicated pregnancies were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Monocytes from women with PE or FGR exhibited increased IL\u201010 secretion and decreased IL\u20101\u03b2 and GM\u2010CSF secretion in response to LPS. While TNF\u03b1 secretion was not significantly different in cultures of control monocytes versus those from complicated pregnancies with or without LPS exposure, monocytes from complicated pregnancies had significantly decreased levels of H3K4me3 associated with <jats:italic>TNF<\/jats:italic> promoter sequences. Cluster quantification and pathway analysis of differentially expressed genes revealed an increased proportion of anti\u2010inflammatory myeloid cells and a lower proportion of inflammatory non\u2010classical monocytes among the circulating monocyte population in women with PE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Monocytes from women with PE and FGR exhibit an immune tolerance phenotype before initiation of labor. Further investigation is required to determine whether this tolerogenic phenotype persists after the affected pregnancy and contributes to increased risk of subsequent disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13908","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T10:40:40Z","timestamp":1723200040000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Maternal Innate Immune Reprogramming After Complicated Pregnancy"],"prefix":"10.1111","volume":"92","author":[{"given":"Nakeisha A.","family":"Lodge\u2010Tulloch","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences Queen's University  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