Elevation of inducible nitric oxide synthase activity in human endometrium during menstruation.

Nitric oxide (NO) is a known agonist of programmed cell death (apoptosis). In order to discover its potential role during menstrual shedding, a process associated with extensive apoptosis, we evaluated activity and mRNA levels of the inducible and constitutive isoforms of NO synthase (NOS) in endometrial specimens of the proliferative (n = 11), late-secretory (n = 7), and menstrual (n = 17) phase of the cycle. These levels were compared with the proportion of apoptotic cells by detection of histochemically labeled DNA fragments. Inducible NOS (iNOS) activity during menstruation was six times that of the proliferative or late-secretory phase (p < 0.05), whereas constitutive NOS activity remained unchanged. Competitive reverse transcription-polymerase chain reaction revealed 146% and 77% increases of iNOS mRNA expression in the late-secretory and menstrual phases, respectively, compared to the proliferative phase (p < 0.05), whereas constitutive NOS mRNA expression remained constant. Inducible NOS immunostaining was restricted to epithelial cells, whereas constitutive NOS immunostainig was confined to vascular endothelia. In addition, the proportion of apoptotic cells within the glands of late-secretory or menstrual endometrium was twice that of the proliferative phase (p < 0.05). We conclude that local production of NO is involved in the signal transduction mechanisms leading to endometrial breakdown during menstruation.

[The role of nitric oxide in reproduction]. / Die Rolle des Stickstoffmonoxids bei der Reproduktion.

Nitrix oxide (NO) is a highly reactive and short-lived radical (half-life time: 10-12 s), which is derived from L-arginine by the NO synthases (NOS) in several organ systems. The release of NO by endothelial cells leads to rapid relaxation of vascular smooth muscle cells, whereas release by several neuronal cells causes neurotransmission. When NOS is actively induced in immune cells or certain epithelia it causes cytotoxicity and/or apoptosis of these cells. In the reproductive organs NO is now considered to be an important trigger molecule for several physiological mechanisms. Follicular synthesized NO is involved in rupture of the follicle during ovulation. Moreover, NO participates in the acrosome reaction of spermatozoa during capacitation. Apoptosis and collagenolysis of the functional endometrium may be involved in endometrial shedding during menstruation. Since NO induces both apoptosis and collagenolysis, the newly discovered production of NO in late secretory endometrium could act as a key mechanism in the process of menstrual disintegration of the endometrium. Additionally, NO is necessary to support and maintain the decidualization process and plays a pivotal role in implantation.