{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:11:54Z","timestamp":1780344714916,"version":"3.54.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1R01HD100729"],"award-info":[{"award-number":["1R01HD100729"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>This study determined if exosomes from ectocervical epithelial (ECTO) cells infected with <jats:italic>Ureaplasma parvum (U. parvum)<\/jats:italic> can carry bacterial antigens and cause inflammation at the feto-maternal interface using two organ-on-chip devices, one representing the vagina-cervix-decidua and another one mimicking the feto-maternal interface, and whether such inflammation can lead to preterm birth (PTB). Exosomes from <jats:italic>U. parvum<\/jats:italic>-infected ECTO cells were characterized using cryo-electron microscopy, nanoparticle tracking analysis, Western blot, and Exoview analysis. The antigenicity of the exosomes from <jats:italic>U. parvum<\/jats:italic>-infected ECTO cells was also tested using THP-1 cells and our newly developed vagina-cervix-decidua organ-on-a-chip (VCD-OOC) having six microchannel-interconnected cell culture chambers containing cells from the vagina, ectocervical, endocervical, transformation zone epithelia, cervical stroma, and decidua. The VCD-OOC was linked to the maternal side of our previously developed feto-maternal interface organ-on-a-chip (FMi-OOC). Cell culture media were collected after 48\u00a0h to determine the cytokine levels from each cell line <jats:italic>via<\/jats:italic> ELISA. For physiological validation of our <jats:italic>in vitro<\/jats:italic> data, high-dose exosomes from <jats:italic>U. parvum<\/jats:italic>-infected ECTO cells were delivered to the vagina of pregnant CD-1 mice on E15. Mice were monitored for preterm birth (PTB, &amp;lt; E18.5\u00a0days). Exosomes from ECTO cells infected with <jats:italic>U. parvum<\/jats:italic> (UP ECTO) showed significant downregulation of exosome markers CD9, CD63, and CD81, but contained multiple banded antigen (MBA), a <jats:italic>U. parvum<\/jats:italic> virulence factor. Monoculture experiments showed that exosomes from UP ECTO cells delivered MBA from the host cell to uninfected endocervical epithelial cells (ENDO). Moreover, exposure of THP-1 cells to exosomes from UP ECTO cells resulted in increased IL-8 and TNF\u03b1 and reduced IL-10. The OOC experiments showed that low and high doses of exosomes from UP ECTO cells produced a cell type-specific inflammatory response in the VCD-OOC and FMi-OOC. Specifically, exosomes from UP ECTO cells increased pro-inflammatory cytokines such as GM-CSF, IL-6, and IL-8 in cervical, decidual, chorion trophoblast, and amnion mesenchymal cells. The results from our OOC models were validated in our <jats:italic>in vivo<\/jats:italic> mice model. The inflammatory response was insufficient to promote PTB. These results showed the potential use of the VCD-OOC and FMi-OOC in simulating the pathophysiological processes <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fcell.2022.931609","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T04:27:47Z","timestamp":1660537667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Exosomes from Ureaplasma parvum-infected ectocervical epithelial cells promote feto-maternal interface inflammation but are insufficient to cause preterm delivery"],"prefix":"10.3389","volume":"10","author":[{"given":"Ourlad Alzeus G.","family":"Tantengco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enkhtuya","family":"Radnaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananth Kumar","family":"Kammala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungjin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Mark B.","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arum","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"237ra65","DOI":"10.1126\/scitranslmed.3008599","article-title":"The placenta harbors a unique microbiome","volume":"6","author":"Aagaard","year":"2014","journal-title":"Sci. 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