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This study developed a six\u2010chamber vagina\u2010cervix\u2010decidua\u2010organ\u2010on\u2010a\u2010chip (VCD\u2010OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD\u2010OOC were characterized by morphology and immunostaining for cell\u2010specific markers. We transferred the media from the decidual cell chamber of the VCD\u2010OOC to decidual cell chamber in feto\u2010maternal interface organ\u2010on\u2010a\u2010chip (FMi\u2010OOC), which contains the fetal membrane layers. An ascending\n                    <jats:italic>Ureaplasma parvum<\/jats:italic>\n                    infection was created in VCD\u2010OOC.\n                    <jats:italic>U. parvum<\/jats:italic>\n                    was monitored for 48\u2009h post\u2010infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending\n                    <jats:italic>U. parvum<\/jats:italic>\n                    infection model of PTB was developed using CD\u20101 mice. The cell morphology and expression of cell\u2010specific markers in the VCD\u2010OOC mimicked those seen in lower genital tract tissues.\n                    <jats:italic>U. parvum<\/jats:italic>\n                    reached the cervical epithelial cells and decidua within 48\u2009h and did not cause cell death in VCD\u2010OOC or FMi\u2010OOC cells.\n                    <jats:italic>U. parvum<\/jats:italic>\n                    infection promoted minimal inflammation, while the combination of\n                    <jats:italic>U. parvum<\/jats:italic>\n                    and LPS promoted massive inflammation in the VCD\u2010OOC and FMi\u2010OOC cells. In the animal model,\n                    <jats:italic>U. parvum<\/jats:italic>\n                    vaginal inoculation of low\u2010dose\n                    <jats:italic>U. parvum<\/jats:italic>\n                    did not result in PTB, and even a high dose had only some effects on PTB (20%). However, intra\u2010amniotic injection of\n                    <jats:italic>U. parvum<\/jats:italic>\n                    resulted in 67% PTB. We report the colonization of\n                    <jats:italic>U. parvum<\/jats:italic>\n                    in various cell types; however, inconsistent, and low\u2010grade inflammation across multiple cell types suggests poor immunogenicity induced by\n                    <jats:italic>U. parvum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1096\/fj.202200872r","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T04:56:54Z","timestamp":1663217814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Modeling ascending\n                    <i>Ureaplasma parvum<\/i>\n                    infection through the female reproductive tract using vagina\u2010cervix\u2010decidua\u2010organ\u2010on\u2010a\u2010chip and feto\u2010maternal interface\u2010organ\u2010on\u2010a\u2010chip"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-8837","authenticated-orcid":false,"given":"Ourlad Alzeus G.","family":"Tantengco","sequence":"first","affiliation":[{"name":"Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston  Galveston Texas USA"},{"name":"Biological Models Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine University of the Philippines Manila  Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8392-2833","authenticated-orcid":false,"given":"Lauren S.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston  Galveston Texas 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