{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:23:02Z","timestamp":1781886182177,"version":"3.54.5"},"reference-count":84,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T00:00:00Z","timestamp":1688774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD098867"],"award-info":[{"award-number":["R01 HD098867"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD102318"],"award-info":[{"award-number":["R01 HD102318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with <jats:italic>Lactobacillus<\/jats:italic>\u2010deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either <jats:italic>Gardnerella vaginalis<\/jats:italic> and <jats:italic>Mobiluncus mulieris<\/jats:italic> alone is sufficient to induce maternal\u2010fetal inflammation and induce sPTB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>C56\/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 10<jats:sup>8<\/jats:sup> colony\u2010forming units of <jats:italic>G. vaginalis<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a030), <jats:italic>M. mulieris<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a017), or <jats:italic>Lactobacillus crispatus<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a016). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6\u00a0h post\u2010infusion for analysis of bacterial growth and cytokine\/chemokine expression in maternal and fetal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six hours following intrauterine inoculation with <jats:italic>G. vaginalis<\/jats:italic>, <jats:italic>M. mulieris<\/jats:italic>, or <jats:italic>L. crispatus<\/jats:italic>, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (10<jats:sup>8<\/jats:sup> CFU\/animal) of <jats:italic>G. vaginalis<\/jats:italic> was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with <jats:italic>L. crispatus<\/jats:italic> or <jats:italic>M. mulieris<\/jats:italic> at 10<jats:sup>8<\/jats:sup> CFU\/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite inducing an immune response, intrauterine infusion of live <jats:italic>G. vaginalis<\/jats:italic> or <jats:italic>M. mulieris<\/jats:italic> is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13749","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T09:39:54Z","timestamp":1688809194000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intrauterine colonization with <i>Gardnerella vaginalis<\/i> and <i>Mobiluncus mulieris<\/i> induces maternal inflammation but not preterm birth in a mouse model"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-9812","authenticated-orcid":false,"given":"Andrea","family":"Joseph","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences Icahn School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2572-1002","authenticated-orcid":false,"given":"Emma L.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Center for Research on Reproduction and Women's Health University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briana","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Center for Research on Reproduction and Women's Health University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Guan","sequence":"additional","affiliation":[{"name":"Center for Research on Reproduction and Women's Health University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Anton","sequence":"additional","affiliation":[{"name":"Center for Research on Reproduction and Women's Health University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal A.","family":"Elovitz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences Icahn School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60820\u20104"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)60560\u20101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.204"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.6.728"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.11.008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(08)60074\u20104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00574"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005183422007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109378(92)91609\u2010e"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0143\u20104004(80)80005\u20101"},{"issue":"4","key":"e_1_2_9_13_1","first-page":"622","article-title":"Histologic chorioamnionitis and preterm delivery in different patient populations","volume":"75","author":"Mueller\u2010Heubach E","year":"1990","journal-title":"Obstet Gynecol"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2000.109035"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0020\u20107292(00)00280\u20100"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002611107"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564\u2010022\u201001083\u20102"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew026"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.10.019"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028620\u20101"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.05.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2684"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2006.12.005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512283332604"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.1.176\u2010186.1994"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.308.6924.295"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109378(93)90157\u2010e"},{"issue":"2","key":"e_1_2_9_28_1","first-page":"173","article-title":"Bacterial vaginosis in early pregnancy and pregnancy outcome","volume":"80","author":"Kurki T","year":"1992","journal-title":"Obstet Gynecol"},{"issue":"1","key":"e_1_2_9_29_1","first-page":"89","article-title":"Relationships of vaginal Lactobacillus species, cervical Chlamydia trachomatis, and bacterial vaginosis to preterm birth","volume":"71","author":"Martius J","year":"1988","journal-title":"Obstet Gynecol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1986.03380140069024"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2018.12.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010017\u20100999\u2010x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705899114"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009285\u20109"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522\u2010020\u201000162\u20108"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010018\u20100502\u20108"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010016\u20100223\u20109"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag1026"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12106"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049\u20102618\u20102\u201018"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00615"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810133191503"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006250\u2010198602000\u201000013"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20100528.1989.tb02430.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992287101000907"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2004.10.009"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010394381\u20101.00001\u20105"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpm\u20102019\u20100297"},{"key":"e_1_2_9_49_1","first-page":"41","article-title":"The bacteriology of Gardnerella vaginalis","volume":"86","author":"Taylor\u2010Robinson D","year":"1984","journal-title":"Scand J Urol Nephrol Suppl"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1989.tb00752.x"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.65118\u20100"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010022\u201001317\u2010"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02181"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2019.102127"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719111398498"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2011.02.011"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)63567\u20105"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000191141.21932.b6"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2009.06.013"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00797\u201020"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719108325508"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/jmf.14.1.57.64"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001385"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109378(95)90503\u20100"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2017.02.002"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2003.10.700"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.593802"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0002\u20109378(12)90858\u20103"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.127129"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1071\u20105576(99)00013\u20101"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100897.2009.00743.x"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100897.2010.00848.x"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jp.7211290"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2020.101146"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.5.1668S"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1179\/096805104225006129"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01965\u201007"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00627\u201013"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284\u2010022\u201002771\u20102"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.01.014"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.05.015"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12102"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00153.2009"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191524"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP\u201021\u20100308"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:18:18Z","timestamp":1692267498000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,8]]},"references-count":84,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1111\/aji.13749"],"URL":"https:\/\/doi.org\/10.1111\/aji.13749","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,8]]},"assertion":[{"value":"2023-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13749"}}