Analysis on tyrosinekinase receptor expression and tubal infertility

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(study1) We analyzed histological and physiological changes in the rabbit oviduct at various time-points from 30 min to 14 day after ligation of both ends of oviduct. In the first 3days, the blood flow decreased, and TUNEL positive epithelial cells and NO level in the oviduct fluid increased. L-NAME injection reduced NO level and the accumulation of fluid. However, L-NAME increased TUNEL positive smooth muscle cells. These results indicated that the rapid increase in NO level after ligation may play a major role in the tissue injury and remodeling in rabbit oviduct. (study2) We established a uterine ischemia-reperfusion model in mice to investigate the pathological changes in the uterus and oviduct. Ischemia induced apoptosis in endometrium and oviduct. The pathological features similar to those seen in the human endometrium during menstruation. The expression levels of TNF α mRNAs in uterus increased after reperfusion. Apoptosis decreased in TNF-R p55-deficient mice, confirming the important role of TNF α in injury-induced apoptosis. Our model seems suitable for investigating human menstruation and tubal infertility. (study3) We analyzed fertilization and embryonal development with mouse uterine ischemic reperfusion model. In this model, the fertilization rate and embryonal development decreased. However, it was increased after injection of superoxide dismutase. This suggest that oxidative stress is the important factor in embryonal development. This model is useful in study of tubal infertility. (study4) We analyzed tyrosine kinase receptor profiles of mouse normal oviduct and ischemic oviduct. Using degenerated primer RT-PCR, the most characteristic receptor was c-met. C-met was expressed in mouse oviduct after ischemia reperfusion in mRNA and immunohistochemistry. After injection of anti c-met antibody, oviduct regeneration after ischemia was decreased. This suggest that c-met and hepatocyte growth factor was important in the oviduct regeneration.