Hyaluronan in cervical epithelia protects against infection-mediated preterm birth
Yucel Akgul, … , Justin Hanes, Mala Mahendroo
Yucel Akgul, … , Justin Hanes, Mala Mahendroo
Published November 10, 2014
Citation Information: J Clin Invest. 2014;124(12):5481-5489. https://doi.org/10.1172/JCI78765.
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Research Article Reproductive biology

Hyaluronan in cervical epithelia protects against infection-mediated preterm birth

Abstract

Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has long been proposed to play an essential role in disorganization of the collagen-rich extracellular matrix to allow for maximal compliance and dilation of the cervix during the birth process. Here, we show that HA is not essential for increased cervical distensibility during late pregnancy. Rather, cervicovaginal HA plays an unanticipated important role in epithelial barrier protection of the lower reproductive tract. Specifically, HA depletion in the cervix and vagina resulted in inappropriate differentiation of epithelial cells, increased epithelial and mucosal permeability, and strikingly increased preterm birth rates in a mouse model of ascending vaginal infection. Collectively, these findings revealed that although HA is not obligatory for cervical compliance, it is crucial for maintaining an epithelial and mucosal barrier to limit pathogen infiltration of the lower reproductive tract during pregnancy and thereby is protective against infection-mediated preterm birth.

Authors

Yucel Akgul, R. Ann Word, Laura M. Ensign, Yu Yamaguchi, John Lydon, Justin Hanes, Mala Mahendroo

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Figure 3

HA depletion results in aberrant organization and differentiation of cervical epithelia.

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HA depletion results in aberrant organization and differentiation of cer...
Ectocervical sections from term (late d18) WT and Has1/2/3 KO mice were evaluated. Alcian blue stained mucus vacuoles (blue) and nonmucosal cells (pink); arrows denote basal epithelial cells lining the basement membrane. Masson trichrome stained keratin and muscle fibers (red), cytoplasm (pale red), collagen (blue), and nuclei (dark brown/black). E-cadherin (green) was present on the cell surface of epithelial cells. TFF1 (green) immunofluorescence was localized to the mucus present in vacuoles of luminal epithelia and secreted mucus. In E-cadherin and TFF1 images, nuclei were stained with DAPI (blue). 4 cervices per genotype were evaluated for each stain. Scale bars: 20 μm.