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Human Reproduction, Vol. 15, No. suppl_3, pp. 96-111, 2000
© 2000 European Society of Human Reproduction and Embryology

Role of nitric oxide in implantation and menstruation

Kristof Chwalisz1,3 and Robert E. Garfield2

1 Jenapharm GmbH & Co. KG Jena, Germany 2 University of Texas Medical Branch Galveston, Texas, USA

Correspondence: 3To whom correspondence should be addressed at: Women's Health Care, Jenapharm GmbH & Co. KG, Otto-Schott-Strasse 15, 07745 Jena, Germany. E-mail: Kristof.Chwalisz{at}Jenapharm.DE

Nitric oxide (NO) is a major paracrine mediator of various biological processes, including vascular functions and inflammation. In blood vessels, NO is produced by the low-input constitutive endothelial NO synthase (eNOS) andis a potent vasodilator and platelet aggregation inhibitor. The inducible NOS isoform (iNOS) is capable of producing NO at high concentrations which have pro-inflammatory properties. Immunohistochemical and molecular studies of endometrial NOS expression, as well as animal experiments with NOS inhibitors, indicate that NO plays an important role in endometrial functions such as endometrial receptivity, implantation and menstruation. In rodents, both iNOS and eNOS are highly up-regulated in the implantation sites, and NOS inhibitors show synergistic effects with antiprogestins in inhibiting theestablishment of pregnancy. In the human endometrium, eNOS have been localized in the glandular epithelium and in endometrial microvascular endothelium, primarily during the luteal phase. iNOS has been found in the endometrial epithelium during menstruation, in immunocompetent endometrial cells, andin decidualized stromal cells. In primates, NO may be involved in the initiation and maintenance of menstrual bleeding by inducing tissue breakdown and vascular relaxation as well as by inhibiting platelet aggregation. Endometriumderived NO may also play a role in myometrial relaxation during menstruation. These studies open up new applications for NO-donating and -inhibiting agents in uterine disorders. NO donors may be useful in the treatment of dysmenorrhoea and for promoting fertility. Antiprogestins, progesterone receptor modulators and iNOS inhibitors may find applications in the treatment and prevention of abnormal uterine bleeding.

Key words: antiprogestins/dysfunctional bleeding/implantation/nitric oxide/progesterone


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