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Researchers identify key substance that protects against pre-term birth.

Researchers at UT Southwestern Medical Center have identified hyaluronon (HA) as a critical substance made by the body that protects against premature births caused by infection. Pre-term birth from infection is the leading cause of infant mortality in many countries according to the World Health Organization. The opensource study is published in the Journal of Clinical Investigation, and is the first to identify the specific role that HA plays in the reproductive tract.

The team found that HA is required to allow the epithelial lining of the reproductive tract to serve as the first line of defense against bacterial infections.  Because of this action, HA offers cervical protection against the bacterial infections that cause 25 to 40 percent of pre-term births in women.

Hyaluronon is a natural substance found in many tissues, and is both a lubricant and a beneficial component of eyes, joints, and skin. It has long been thought to play an essential role in increasing the cervix’s flexibility during the birth process; however, the study, which was conducted using mouse models, showed that HA is not essential for increased cervical pliability during late pregnancy.

Rather, the substance plays an important barrier role in epithelial cells of the lower reproductive tract and in so doing protects against infection-related pre-term birth. The World Health Organization estimates that 1.09 million children under age 5 die from direct complications of being born prematurely, meaning before the 37th week of pregnancy.

Previous studies by UT Southwestern researchers showed that HA is present in both the cervix and cervical mucus of pregnant women. Next steps include determining the mechanism by which HA affects cervical protection against infection.

The team summise that this study demonstrates that HA plays a crucial role in the epithelial barrier as well as the cervix’s mucus. The next step is to identify exactly how HA protects the cervix, which can have important clinical implications in the effort to reduce infection-mediated pre-term labour.

Source:  UT Southwestern Medical Center

 HA depletion results in aberrant organization and differentiation of cervical epithelia. 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.  Hyaluronan in cervical epithelia protects against infection-mediated preterm birth.  Akgul et al 2014.

HA depletion results in aberrant organization and differentiation of cervical epithelia.
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. Hyaluronan in cervical epithelia protects against infection-mediated preterm birth. Akgul et al 2014.

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