Inflammatory mediators in the cervix, placenta and fetal membranes play a crucial role in human parturition. The aim of this study was to determine whether the upper and lower segments of the myometrium are infiltrated by inflammatory cells during pregnancy and parturition. Myometrial biopsies were obtained from non-pregnant women, and pregnant women at term before and after the onset of spontaneous labour. Subpopulations of inflammatory cells were identified using immunocytochemistry. The intercellular adhesion molecules, 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin were immunolocalized to investigate their involvement in leukocyte accumulation. Histological analysis demonstrated that inflammatory cells, predominantly neutrophils and macrophages, infiltrate human myometrium during spontaneous labour at term. The infiltrate is predominant in the lower uterine segment but is also present in the upper segment. Increased expression of E-selectin was found on the vascular endothelium of biopsies obtained during labour, suggesting a role for this molecule in the accumulation of leukocytes. These results suggest that inflammatory cell infiltration is part of the physiological mechanisms that occur in the myometrium during parturition. Further understanding of this process may suggest new strategies aimed at preventing preterm delivery.

Inflammatory mediators in the cervix, placenta and fetal membranes play a crucial role in human parturition. The aim of this study was to determine whether the upper and lower segments of the myometrium are infiltrated by inflammatory cells during pregnancy and parturition. Myometrial biopsies were obtained from non-pregnant women, and pregnant women at term before and after the onset of spontaneous labour. Subpopulations of inflammatory cells were identified using immunocytochemistry. The intercellular adhesion molecules, 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin were immunolocalized to investigate their involvement in leukocyte accumulation. Histological analysis demonstrated that inflammatory cells, predominantly neutrophils and macrophages, infiltrate human myometrium during spontaneous labour at term. The infiltrate is predominant in the lower uterine segment but is also present in the upper segment. Increased expression of E-selectin was found on the vascular endothelium of biopsies obtained during labour, suggesting a role for this molecule in the accumulation of leukocytes. These results suggest that inflammatory cell infiltration is part of the physiological mechanisms that occur in the myometrium during parturition. Further understanding of this process may suggest new strategies aimed at preventing preterm delivery.

The aim of this study was to investigate the presence of nitric oxide synthase (NOS) in human uterus. Tissues were obtained at operation from 10 women undergoing hysterectomy for benign disease. In-situ hybridization was used to determine the distribution of mRNA for NOS with a 483 bp digoxigenin-labelled antisense riboprobe. Localization of NOS was detected by (i) immunocytochemistry using a monoclonal antibody raised against bovine constitutive endothelial NOS, and (ii) NADPH diaphorase, which has been suggested to co-localize with brain NOS. Messenger RNA for NOS was detected in endometrium and myometrium from nine of 10 women, predominantly in endometrial glandular epithelium and stroma and myometrial blood vessels. NOS-like immunoreactivity was seen in endometrial stroma and myometrial blood vessels, whereas NADPH diaphorase activity was localized mainly to endometrial glandular epithelium and myometrial blood vessels. These studies suggest that different forms of constitutive NOS are present in human endometrium and myometrium, and that nitric oxide may play a role in the paracrine control of the uterine vascular bed.

Immunocytochemistry was used to localize endothelial (eNOS) and inducible (iNOS) nitric oxide synthase in human uterine tissues collected at various stages of the menstrual cycle, after exposure to exogenous progestagens, and in early pregnancy. Endothelial NOS-like immunoreactivity was detected in all specimens in endothelial cells lining blood vessels in the myometrium and endometrium, and in endometrial glandular epithelial cells. Inducible NOS-like immunoreactivity was also demonstrated in glandular epithelial cells. For both eNOS and iNOS there was considerable variation in the intensity of epithelial cell staining between samples, which was not related to the stage of the menstrual cycle at which the tissue was collected. Messenger RNA for eNOS and iNOS was detected by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA purified from isolated endometrial gland fragments. Immunoreactivity for eNOS and iNOS was not present in endometrial stroma throughout the menstrual cycle, but iNOS-like immunoreactivity was seen in decidualized stromal cells both following treatment with exogenous progestagen (intrauterine L-norgestrel) and in tissues obtained in the first trimester of pregnancy. The detection of protein and mRNA for eNOS and iNOS in normal human endometrium suggests that NO may play a role in the local control of endometrial function.

Animal studies have suggested that nitric oxide, a smooth muscle relaxant, is a fundamental mediator in the initiation of parturition. The purpose of this study was to test the hypothesis that the onset of human labour is associated with a reduction in the activity of the enzyme nitric oxide synthase (NOS), within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were collected during Caesarean section from 11 women before and 11 women after the onset of labour at term. Immunocytochemistry was used to localize each of the three isoforms of NOS (endothelial NOS, brain NOS, and inducible NOS) in each of these tissues and the intensity of staining was qualitatively assessed. NOS enzyme activity was determined in homogenates of frozen myometrium, placenta and fetal membranes (with attached decidua), by measuring conversion of radio-labelled L-arginine to L-citrulline. Each of the three isoforms of NOS was localized in each of the tissues. We found no difference in either the expression or enzyme activity of NOS in myometrium, placenta or fetal membranes before and during labour at term. These results suggest that, in contrast to animal studies, a decrease in NOS enzyme activity may not be involved in the onset of parturition at term in the human.