Glycobiology Advance Access published online on August 18, 2004
Glycobiology, doi:10.1093/glycob/cwh137
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1 Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
* To whom correspondence should be addressed. E-mail: mala.mahendroo{at}utsouthwestern.edu.
The uterine cervix, in preparation for birth, undergoes a remarkable transformation from a closed, rigid structure to a distensible, remodeled configuration that stretches to allow passage of a fetus. Cervical ripening requires changes in the composition and structure of the extracellular matrix. These include an increase in the glycosaminoglycan, hyaluronan (HA), prior to parturition. Here we show that the increase in cervical HA with advancing gestation correlates with the temporal increase in transcription of hyaluronan synthase 2 (HAS2) in the mouse. On gestation day 18, one day prior to birth, HAS2 transcripts are most abundant and begin to decline after birth. The steroid 5
Revised August 9, 2004
Accepted August 9, 2004
ORIGINAL ARTICLES
Regulation of hyaluronan expression during cervical ripening
2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
3 Department of Pathology and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
4 Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Abstract 
-reductase type 1 deficient mouse, which fails to undergo cervical remodeling, has decreased expression of HAS2 mRNA and decreased tissue HA. HAS2 transcripts are expressed by cervical epithelium while HA is localized to the matrix surrounding the stroma and to a lesser extent around the epithelium. HAS2 expression is suppressed in mice treated with progesterone. The mRNA expression levels of HA metabolizing enzymes, hyaluronidase 1 and hyaluronidase 2 were unchanged during pregnancy, but increased after birth. Thus, the net increase in HA content at term correlates with increased transcription of HAS2. Regulation of HA content is conserved in women as HAS2 transcripts are upregulated in cervices of women in labor as compared to pregnant women not in labor. These results provide insights into the regulation of HA biosynthesis during cervical ripening and underscore the physiological role HA plays in this essential process.-reductase type 1.
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