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The current study evaluated whether direct (myometrial) or indirect (decidual) TLR9 engagement enhances human myometrial contractility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Toll\u2010like receptor 9 expression and cellular localization were surveyed by immunohistochemistry of placenta, fetal membranes, and myometrium in term (gestational age [GA]: &gt;37\u00a0weeks) labor (TL, n\u00a0=\u00a07) or term non\u2010labor (TNL, n\u00a0=\u00a07) tissues. Non\u2010pregnant myometrium (n\u00a0=\u00a04) served as reference. TLR9 mRNA expression relative to other TLRs was evaluated through the mining of an RNA\u2010seq dataset and confirmed by RT\u2010PCR. Immortalized human myometrial cells (hTERT\u2010HM) were treated with incremental concentrations of TLR9 agonist ODN2395, TNF\u2010\u03b1, or LPS. Secreted cytokines were quantified by multiplex immunoassay, and contractility was assessed by an in\u2010gel cell contraction assay (n\u00a0=\u00a09). Induction of hTERT\u2010HM contractility was also evaluated indirectly following exposure to conditioned media from primary term decidual cells (n\u00a0=\u00a04) previously stimulated with ODN2395.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Toll\u2010like receptor 9 immunostaining in placenta and amniochorion was strongest in decidual cells, but unrelated to labor. TLR9 staining intensity was significantly decreased in TL compared with TNL myometrium (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). Although total cfDNA in maternal circulation increased in TL (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.025 vs TNL), difference in cffDNA was non\u2010significant. Myometrial TLR9 mRNA levels were unaffected by contractile status and far less abundant than other pro\u2010inflammatory TLRs. hTERT\u2010HM contractility was enhanced by LPS (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) and TNF\u2010\u03b1 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003), but not by ODN2395 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.345) or supernatant of TLR9\u2010stimulated decidual cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Myometrial and decidual TLR9 are unlikely to directly regulate human parturition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13100","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T18:00:38Z","timestamp":1550080838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Toll\u2010like receptor 9, maternal cell\u2010free DNA and myometrial cell response to CpG oligodeoxynucleotide 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