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A Large Keratan Sulfate Proteoglycan Present in Human Cervical Mucous Appears to Be Involved in the Reorganization of the Cervical Extracellular Matrix at Term

Department of Obstetrics and Gynecology, Freiburg University Medical Center, Freiburg, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Aachen University of Technology, Department of Obstetrics and Gynecology, Aachen University of Technology, Institute of Pathology, Aachen University of Technology, Aachen, Germany; and Institute of Pathology, Humboldt University Berlin, Berlin, Germany; Department of Obstetrics and Gynaecology I, Freiburg University Medical Center, Hugstetter Str. 55, D-79106 Freiburg i. Br., Germany; dfischer{at}frk.uk1.uni-freiburg.de

Astrid Kuth, PhD

Matthias Winkler, MD

Stefan Handt, MD

Steffen Hauptmann, MD

Werner Rath, MD

Hans-Dieter Haubeck, MD

Department of Obstetrics and Gynecology, Freiburg University Medical Center, Freiburg, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Aachen University of Technology, Department of Obstetrics and Gynecology, Aachen University of Technology, Institute of Pathology, Aachen University of Technology, Aachen, Germany; and Institute of Pathology, Humboldt University Berlin, Berlin, Germany

Objective: To elucidate the function of keratan sulfate proteoglycan (KS-PG) in the human uterine cervix, we analyzed its distribution with respect to physiologic conditions.

Methods: Immunohistochemistry was used to localize KS bearing proteoglycans (mAb 5D4) and decorin (mAb 6B6) in the lower uterine segment. Proteins present in cervical mucous were labeled with biotin, glycosaminoglycan chains were digested enzymatically, and the samples were analyzed by Western blot.

Results: Decorin was detected throughout the extracellular matrix, in tissues from menstruating nonpregnant women, in early pregnancy, from women who had cesarean at term, at postpartum hysterectomy, and from postmenopausal women. In menstruating nonpregnant women, in early pregnancy (first trimester), and in postmenopausal women, KS-PG was detectable only in epithelial, mucous-producing cells. Interestingly, in samples obtained either at the time of cesarean at term (lower uterine segment) or after postpartal hysterectomy, KS-PG was detectable throughout the extracellular matrix, indicating that the expression of KS-PG is associated with reorganization of the tissue. Biochemical analysis of the KS present in mucous revealed a core protein in the range of 220 kDa, suggesting an identity with the large KS-PG described previously.

Conclusion: At parturition, a large KS-PG, which is virtually exclusively present in the cervical mucous of either early or nonpregnant women, was detected in the extracellular matrix. This finding indicates that cervical ripening is accompanied not only by quantitative but also by qualitative changes in the composition of the extracellular matrix.

Key Words: Cervical mucous • extracellular matrix • human uterine cervix • keratan sulfate proteoglycan • parturition • pregnancy

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