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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Nature Publishing Group
2017
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Online Access: | http://hdl.handle.net/1721.1/112634 https://orcid.org/0000-0003-0037-5999 https://orcid.org/0000-0001-8260-338X |
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author | Conroy, K. Pagidas, K. Snegovskikh, V. House, M. Smith-Dupont, K. B. Wagner, Caroline E Witten, Jacob Julian Seid Rudoltz, Hannah R. Ribbeck, Katharina |
author2 | Massachusetts Institute of Technology. Center for Environmental Health Sciences |
author_facet | Massachusetts Institute of Technology. Center for Environmental Health Sciences Conroy, K. Pagidas, K. Snegovskikh, V. House, M. Smith-Dupont, K. B. Wagner, Caroline E Witten, Jacob Julian Seid Rudoltz, Hannah R. Ribbeck, Katharina |
author_sort | Conroy, K. |
collection | MIT |
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-A nd 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-A nd 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. |
first_indexed | 2024-09-23T08:43:53Z |
format | Article |
id | mit-1721.1/112634 |
institution | Massachusetts Institute of Technology |
last_indexed | 2024-09-23T08:43:53Z |
publishDate | 2017 |
publisher | Nature Publishing Group |
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spelling | mit-1721.1/1126342022-09-23T14:10:46Z Probing the potential of mucus permeability to signify preterm birth risk Conroy, K. Pagidas, K. Snegovskikh, V. House, M. Smith-Dupont, K. B. Wagner, Caroline E Witten, Jacob Julian Seid Rudoltz, Hannah R. Ribbeck, Katharina Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Smith-Dupont, K. B. Wagner, Caroline E Witten, Jacob Julian Seid Rudoltz, Hannah R. Ribbeck, Katharina 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-A nd 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-A nd 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. National Science Foundation (U.S.) (Award DMR-0819762) National Science Foundation (U.S.) (Award 1122374) 2017-12-07T18:36:41Z 2017-12-07T18:36:41Z 2017-09 2017-02 2017-12-06T20:44:57Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/112634 Smith-Dupont, K. B. et al. “Probing the Potential of Mucus Permeability to Signify Preterm Birth Risk.” Scientific Reports 7, 1 (September 2017) © 2017 The Author(s) https://orcid.org/0000-0003-0037-5999 https://orcid.org/0000-0001-8260-338X http://dx.doi.org/10.1038/s41598-017-08057-z Scientific Reports Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
spellingShingle | Conroy, K. Pagidas, K. Snegovskikh, V. House, M. Smith-Dupont, K. B. Wagner, Caroline E Witten, Jacob Julian Seid Rudoltz, Hannah R. Ribbeck, Katharina 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 |
url | http://hdl.handle.net/1721.1/112634 https://orcid.org/0000-0003-0037-5999 https://orcid.org/0000-0001-8260-338X |
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