Role of nitric oxide in implantation and menstruation

Nitric oxide (NO) is a major paracrine mediator of various biological proce sses, including vascular functions and inflammation. In blood vessels, NO i s produced by the low-input constitutive endothelial NO synthase (eNOS) and is 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 inhi bitors, indicate that NO plays an important role in endometrial functions s uch as endometrial receptivity, implantation and menstruation. In rodents, both iNOS and eNOS are highly up-regulated in the implantation sites, and N OS inhibitors show synergistic effects with antiprogestins in inhibiting th e establishment of pregnancy. In the human endometrium, eNOS have been loca lized in the glandular epithelium and in endometrial microvascular endothel ium, primarily during the luteal phase. iNOS has been found in the endometr ial epithelium during menstruation, in immunocompetent endometrial cells, a nd in decidualized stromal cells. In primates, NO may be involved in the in itiation and maintenance of menstrual bleeding by inducing tissue breakdown and vascular relaxation as well as by inhibiting platelet aggregation. End ometrium-derived NO may also play a role in myometrial relaxation during me nstruation. These studies open up new applications for NO-donating and-inhi biting agents in uterine disorders. NO donors may be useful in the treatmen t of dysmenorrhoea and for promoting fertility. Antiprogestins, progesteron e receptor modulators and iNOS inhibitors may find applications in the trea tment and prevention of abnormal uterine bleeding.