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Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced...

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Autores principales: Pavlidis, Ioannis, Spiller, Owen B., Sammut Demarco, Gabriella, MacPherson, Heather, Howie, Sarah E. M., Norman, Jane E., Stock, Sarah J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954262/
https://www.ncbi.nlm.nih.gov/pubmed/31924800
http://dx.doi.org/10.1038/s41467-019-14089-y
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author Pavlidis, Ioannis
Spiller, Owen B.
Sammut Demarco, Gabriella
MacPherson, Heather
Howie, Sarah E. M.
Norman, Jane E.
Stock, Sarah J.
author_facet Pavlidis, Ioannis
Spiller, Owen B.
Sammut Demarco, Gabriella
MacPherson, Heather
Howie, Sarah E. M.
Norman, Jane E.
Stock, Sarah J.
author_sort Pavlidis, Ioannis
collection PubMed
description Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth.
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spelling pubmed-69542622020-01-13 Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice Pavlidis, Ioannis Spiller, Owen B. Sammut Demarco, Gabriella MacPherson, Heather Howie, Sarah E. M. Norman, Jane E. Stock, Sarah J. Nat Commun Article Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth. Nature Publishing Group UK 2020-01-10 /pmc/articles/PMC6954262/ /pubmed/31924800 http://dx.doi.org/10.1038/s41467-019-14089-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pavlidis, Ioannis
Spiller, Owen B.
Sammut Demarco, Gabriella
MacPherson, Heather
Howie, Sarah E. M.
Norman, Jane E.
Stock, Sarah J.
Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title_full Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title_fullStr Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title_full_unstemmed Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title_short Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
title_sort cervical epithelial damage promotes ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954262/
https://www.ncbi.nlm.nih.gov/pubmed/31924800
http://dx.doi.org/10.1038/s41467-019-14089-y
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