Molecular Human Reproduction, Vol. 5, No. 10, 973-982,
October 1999
© 1999 European Society of Human Reproduction and Embryology
Molecular aspects of pregnancy |
Nitric oxide donors stimulate prostaglandin F2
and inhibit thromboxane B2 production in the human cervix during the first trimester of pregnancy
1 Department of Obstetrics and Gynaecology, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER, 2 Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW and 3 Medical Research Council Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9ET, UK
Abstract
Nitric oxide (NO) donors are capable of ripening the human cervix during pregnancy. The purpose of this study was to examine how NO donors may be involved in this process. Cervical biopsies were obtained from pregnant women randomized to receive isosorbide mononitrate (n = 10) or no treatment (n = 10) prior to suction termination. Enzyme-linked immunosorbent assays (ELISA) were performed on culture supernatant for interleukin (IL)-1, IL-6, IL-8, IL-10, IL-15, tumour necrosis factor-
, monocyte chemotractant protein-1 and prostaglandin metabolites. Immunohistochemistry was performed to localize these cytokines, cyclooxygenase (COX)-1, COX-2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription–polymerase chain reaction (RT–PCR) to identify COX-1 and COX-2 expression. Biopsies treated with the NO donor isosorbide mononitrate (IMN) produced significantly greater amounts of prostaglandin F2 in culture and lower amounts of thromboxane B2 than controls (572.8 versus 34.9 pg/ml, P < 0.05; 53.3 pg/ml versus 530.9 pg/ml, P < 0.01 respectively). The release of other prostaglandins and of cytokines was not affected by treatment with NO. Inflammatory mediators were localized to cervical tissue and COX-1 and COX-2 expression was confirmed by RT–PCR. In conclusion, the mechanism of NO donor-induced cervical ripening during pregnancy may be mediated in part via increased prostaglandin F2 synthesis.
cervical ripening/cytokines/nitric oxide/pregnancy/prostaglandin
Notes
4 To whom correspondence should be addressed
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