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Hum. Reprod. Advance Access originally published online on May 9, 2006
Human Reproduction 2006 21(8):2180-2184; doi:10.1093/humrep/del141
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Mifepristone-induced nitric oxide release and expression of nitric oxide synthases in the human cervix during early pregnancy

Mervi Väisänen-Tommiska1, Ralf Butzow1,2, Olavi Ylikorkala1,3 and Tomi S. Mikkola1

1 Department of Obstetrics and Gynecology and 2 Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, FIN-00029 HUS, Helsinki, Finland. E-mail: olavi.ylikorkala{at}hus.fi

BACKGROUND: Nitric oxide (NO) is a factor in cervical ripening, perhaps under the control of progesterone. We studied the effects of the antiprogesterone mifepristone on the release of NO and on the expression of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) in the uterine cervix of women in early pregnancy. METHODS: Thirteen women were treated with oral mifepristone (200 mg), and 15 women were studied as controls. Cervical fluid samples were collected before treatment then hourly up to 3 h, and the samples were assayed for the concentration of nitric oxide metabolites (NOx). In addition, cervical biopsy samples from six women treated with mifepristone and from six controls were assessed for iNOS and eNOS by immunohistochemistry and Western blotting. RESULTS: In 1–3 h, mifepristone induced 7.4- to 17.2-fold elevations in cervical fluid NOx concentrations; no change was seen in the controls. The expression of both iNOS and eNOS was detected in the cervical cells. The expression of cervical iNOS was strong in five of the six women treated with mifepristone but was not strong in any of the six control women. CONCLUSION: This is the first study to show that mifepristone stimulates the release of NO and the expression of iNOS in cervical cells of women in early pregnancy. This may be one mechanism by which mifepristone initiates cervical ripening.

Key words: antiprogestin/cervical ripening/eNOS/iNOS/nitrate/nitrite


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