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Mol. Hum. Reprod. Advance Access originally published online on September 30, 2005
Molecular Human Reproduction 2005 11(9):659-665; 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.

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

Maki Takemura1, Hiroaki Itoh1,5, Norimasa Sagawa2, Shigeo Yura1, Daizo Korita1, Kazuyo Kakui1, Makoto Kawamura1, Naoyoshi Hirota3, Hiroshi Maeda4 and Shingo Fujii1

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

5 To whom correspondence should be addressed at: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: ihiroaki{at}kuhp.kyoto-u.ac.jp

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 (CxF) 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 CxF 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.

Key words: cervical ripening/hyaluronan synthase/hyaluronan/mechanical stretch/uterine cervix


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K. R. Ingram, A. K. T. Wann, C. K. Angel, P. J. Coleman, and J. R. Levick
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