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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Main Authors: Conroy, K., Pagidas, K., Snegovskikh, V., House, M., Smith-Dupont, K. B., Wagner, Caroline E, Witten, Jacob Julian Seid, Rudoltz, Hannah R., Ribbeck, Katharina
Other Authors: Massachusetts Institute of Technology. Center for Environmental Health Sciences
Format: Article
Published: Nature Publishing Group 2017
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.
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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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