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Hum. Reprod. Advance Access published online on May 9, 2006
Human Reproduction, 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
Received February 9, 2006
Revised March 29, 2006
Accepted April 4, 2006

Article

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

Mervi Väisänen-Tommiska 1, Ralf Butzow 2, Olavi Ylikorkala 3 *, and Tomi S. Mikkola 1

1 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
2 Department of Obstetrics and Gynecology; Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
3 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, FIN-00029 HUS, Helsinki, Finland

* To whom correspondence should be addressed.
Olavi Ylikorkala, E-mail: olavi.ylikorkala{at}hus.fi


  Abstract

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 human cervix. This may be one mechanism by which mifepristone initiates cervical ripening.

Keywords: antiprogestin/cervical ripening/eNOS/iNOS/nitrate/nitrite.
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