Copper-T intrauterine device and levonorgestrel intrauterine system: biological bases of their mechanism of action.

Tryptase and chymase immunolocalization techniques have been used to examine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in 107 endometrial specimens that represented every day of the human menstrual cycle. MCs were identified in the endometrium in all stages of the menstrual cycle; similar MC numbers were observed for the functionalis, basalis, and muscularis. Extensive MC activation/degranulation, as judged by extracellular tryptase, was a common feature of the functionalis in specimens sampled just prior to and during menstruation. MC activation was also prominent in the functionalis at times coincident with recognized stromal edema. MCs of the functionalis did not contain chymase; all stained for tryptase and represent the MCT phenotype. By contrast, the basalis and muscularis showed a proportion of MCs containing both tryptase and chymase, MCTC. One important function for extracellular MC tryptase and chymase is their ability to activate precursor forms of the matrix metalloproteinases, enzymes recognized as instrumental in stromal degradation. Quantitative analysis of MC numbers, expressed relative to stromal cell numbers/mm2, indicated no major changes during the menstrual cycle, although changes in MC morphology, granule content, and activation/degranulation were recognized for specific stages. Eosinophils, detected with monoclonal antibodies EG1 and EG2, were absent from extravascular sites between Days 5 and 26 but showed local accumulations just prior to and during menstruation. Since MCs and eosinophils between them contain a variety of potent mediators, it seems likely that both cell types assume important functional roles in relation to tissue and vascular remodeling associated with endometrial physiology.

/pdf/mast-cell-and-eosinophil-distribution-and-activation-in-47z2pmwxc8.pdf

Mast cell and eosinophil distribution and activation in human endometrium throughout the menstrual cycle.

Endometrial morphological changes in IUD users: A review

Data from the 1983 US Cancer and Steroid Hormones (CASH) Study (a large multicenter population-based case-control study) were analyzed to reveal the relationship between IUD use and endometrial cancer. Interviews were conducted with 673 of the 905 cases and histologic information and slides were reviewed for 575 of these with the result that 437 were found to meet the criteria for primary epithelial malignant neoplasm of the endometrium. Of the 5698 randomly selected controls 83% were interviewed and data from 3200 were analyzed. Since three women could not remember whether or not they had used an IUD final analysis was based on 436 cases and 3199 controls. The data were screened for confounding variables using the Mantel-Haenszel procedure logistic regression and multivariate logistic regression. Adjusted odds ratios were estimated for three subtypes of cancer and for the duration of IUD use age at IUD use and time since IUD use. The effect of 21 potential effect modifiers (including age parity age at menarche menopausal status race and education) were also identified. It was found that IUD use was significantly associated with a lower chance of developing endometrial cancer. Only age and parity appreciably reduced the protective effect but the protective effect remained significant after adjustment for age and parity. Duration of use increased the protective effect as did younger ages at first IUD use. Years of education constituted the only statistically significant effect modifier; women with less than 13 year of education were not significantly protected by IUD use. Limitations in the use of the CASH data included the fact that procedures to specifically assist in the recall of IUD use were not incorporated and that information on the type of IUD was not collected. The protective effect of the IUD may be caused by changes in endometrial sensitivity and by a response to circulating estrogen and progesterone induced by the presence of the IUD. The public health significance of these findings lies in the fact that a positive relationship between IUD use and endometrial cancer was so strongly ruled out. These results require further research and replication.

Intra-uterine contraception and the risk of endometrial cancer

BACKGROUND: The detection of significant levels of tryptase in human seminal plasma and follicular fluid and of tryptase-positive mast cells (MCs) in the wall of human Fallopian tubes lead us to hypothesize that tryptase may exert regulatory actions on human spermatozoa. METHODS AND RESULTS: Immunoelectronmicroscopy revealed proteinase-activated receptor 2 (PAR-2) in the membranes of the acrosomal region and midpiece of human spermatozoa. These PAR-2 were functional, as exposure of spermatozoa from healthy men (n = 12) with regular standard semen parameters to human recombinant tryptase significantly decreased motility in a dose- and time-dependent fashion. Motile spermatozoa (WHO a + b) were significantly decreased within 10 min of incubation with 1.000 ng/ml tryptase (P = 0.045). After 30 and 60 min, significant reduction of motility was also observed in the presence of lower tryptase concentrations (100 ng/ml, P = 0.037; 10 ng/ml, P = 0.046). The inhibitory effects of tryptase progressed throughout an observation period of 180 min. Furthermore, tryptase effects were reversible after washing procedures and could be inhibited by pretreatment with anti-tryptase antibody or anti-PAR-2 antiserum. CONCLUSIONS: The observations presented raise the possibility that tryptase directly interacts with human spermatozoa during their migration through the female genital tract. Genital tract MCs and their products may be as yet unrecognized factors involved in human fertility/sterility.

/pdf/mast-cell-sperm-interaction-evidence-for-tryptase-and-2z8uirawv7.pdf

Mast cell–sperm interaction: evidence for tryptase and proteinase‐activated receptors in the regulation of sperm motility

Possible role of mast cells in the mechanism of action of intrauterine contraceptive devices

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Possible role of mast cells in the mechanism of action of intrauterine contraceptive devices