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Probing the potential of mucus permeability to signify preterm birth risk

Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant...

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Autores principales: Smith-Dupont, K. B., Wagner, C. E., Witten, J., Conroy, K., Rudoltz, H., Pagidas, K., Snegovskikh, V., House, M., Ribbeck, K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583328/
https://www.ncbi.nlm.nih.gov/pubmed/28871085
http://dx.doi.org/10.1038/s41598-017-08057-z
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author Smith-Dupont, K. B.
Wagner, C. E.
Witten, J.
Conroy, K.
Rudoltz, H.
Pagidas, K.
Snegovskikh, V.
House, M.
Ribbeck, K.
author_facet Smith-Dupont, K. B.
Wagner, C. E.
Witten, J.
Conroy, K.
Rudoltz, H.
Pagidas, K.
Snegovskikh, V.
House, M.
Ribbeck, K.
author_sort Smith-Dupont, K. B.
collection PubMed
description Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant ovulating (n = 20) and high- (n = 9) and low-risk (n = 16) pregnant women to probes of varying sizes and surface chemistries. We found that the motion of negatively charged, carboxylated microspheres in mucus from pregnant patients was significantly restricted compared to ovulating patients, but not significantly different between high- and low-risk pregnant women. In contrast, charged peptide probes small enough to avoid steric interactions, but sensitive to the biochemical modifications of mucus components exhibited significantly different transport profiles through mucus from high- and low-risk patients. Thus, although both microstructural rearrangements of the components of mucus as well as biochemical modifications to their adhesiveness may alter the overall permeability of the cervical mucus plug, our findings suggest that the latter mechanism plays a dominant role in the impairment of the function of this barrier during preterm birth. We expect that these probes may be readily adapted to study the mechanisms underlying disease progression on all mucosal epithelia, including those in the mouth, lungs, and gut.
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spelling pubmed-55833282017-09-06 Probing the potential of mucus permeability to signify preterm birth risk Smith-Dupont, K. B. Wagner, C. E. Witten, J. Conroy, K. Rudoltz, H. Pagidas, K. Snegovskikh, V. House, M. Ribbeck, K. Sci Rep Article Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant ovulating (n = 20) and high- (n = 9) and low-risk (n = 16) pregnant women to probes of varying sizes and surface chemistries. We found that the motion of negatively charged, carboxylated microspheres in mucus from pregnant patients was significantly restricted compared to ovulating patients, but not significantly different between high- and low-risk pregnant women. In contrast, charged peptide probes small enough to avoid steric interactions, but sensitive to the biochemical modifications of mucus components exhibited significantly different transport profiles through mucus from high- and low-risk patients. Thus, although both microstructural rearrangements of the components of mucus as well as biochemical modifications to their adhesiveness may alter the overall permeability of the cervical mucus plug, our findings suggest that the latter mechanism plays a dominant role in the impairment of the function of this barrier during preterm birth. We expect that these probes may be readily adapted to study the mechanisms underlying disease progression on all mucosal epithelia, including those in the mouth, lungs, and gut. Nature Publishing Group UK 2017-09-04 /pmc/articles/PMC5583328/ /pubmed/28871085 http://dx.doi.org/10.1038/s41598-017-08057-z Text en © The Author(s) 2017 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
Smith-Dupont, K. B.
Wagner, C. E.
Witten, J.
Conroy, K.
Rudoltz, H.
Pagidas, K.
Snegovskikh, V.
House, M.
Ribbeck, K.
Probing the potential of mucus permeability to signify preterm birth risk
title Probing the potential of mucus permeability to signify preterm birth risk
title_full Probing the potential of mucus permeability to signify preterm birth risk
title_fullStr Probing the potential of mucus permeability to signify preterm birth risk
title_full_unstemmed Probing the potential of mucus permeability to signify preterm birth risk
title_short Probing the potential of mucus permeability to signify preterm birth risk
title_sort probing the potential of mucus permeability to signify preterm birth risk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583328/
https://www.ncbi.nlm.nih.gov/pubmed/28871085
http://dx.doi.org/10.1038/s41598-017-08057-z
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