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Mol. Hum. Reprod. Advance Access published online on September 30, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah229
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Published by Oxford University Press [2005] on behalf of the European Society of Human Reproduction and Embryology.
Received July 31, 2005
Accepted August 26, 2005

Article

Cyclic mechanical stretch augments hyaluronan production in cultured human uterine cervical fibroblast cells

Maki Takemura 1, Hiroaki Itoh 1*, Norimasa Sagawa 2, Shigeo Yura 1, Daizo Korita 1, Kazuyo Kakui 1, Makoto Kawamura 1, Naoyoshi Hirota 3, Hiroshi Maeda 4, and Shingo Fujii 1

1 Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan
2 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Edobasi, Tsu, Mie, Research, Nippon Organon KK, Dohjima, Kita-ku, Osaka, Japan
3 Development Division (NH), Nippon Organon KK, Dohjima, Kita-ku, Osaka, Japan
4 Seikagaku Corporation and Central Research Laboratories, Tateno 3-chome, Higashiyamato, Tokyo, Japan

* To whom correspondence should be addressed.
Hiroaki Itoh, E-mail: ihiroaki{at}kuhp.kyoto-u.ac.jp


  Abstract

Hyaluronan (HA) a glycosaminoglycan with high affinity for water molecules stimulates local inflammatory reactions. Parturition causes a dramatic increase in the amount of HA fragments in the uterine cervix, thereby contributing to a rapid softening as well as opening of the cervical canal, i.e. cervical ripening. The aim of this study was to investigate the possible involvement of cyclic distension caused by labour in the augmentation of HA production during cervical ripening. Immunohistochemistry and/or RT-PCR detected hyaluronan synthase (HAS)1, 2 and 3 in samples of human cervical tissue obtained from pregnant women. Labour-like cyclic mechanical stretch for 24, 36 and 48 h significantly enhanced the secretion of HA, from cultured human uterine cervical fibroblast (C x F) cells, 128.7, 151.4 and 173.2%, respectively, concomitant with a significant augmentation of HAS1 (36, 48 h), HAS2 (24, 36 and 48 h) and HAS3 (48 h) mRNA expression. Cyclic mechanical stretch for 12, 36 and 48 h increased molecular size of the HA secreted from C x F cells. In conclusion, cyclic mechanical stretch of the uterine cervix caused by the presenting part of the fetus in labour may contribute to the increase in the secretion of HA during the process of cervical ripening.

Keywords: cervical ripening/hyaluronan synthase/hyaluronan/mechanical stretch/uterine cervix.
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