The Role of Granulocytes in Estrogen-Induced Extracellular Matrix Remodeling in the Endometrium of the Rat Uterus

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Description: Estrogen-mediated remodeling in the extracellular matrix of the uterine endometrium is crucial to the processes that occur in the normal reproductive cycle of this organ. Many studies have indicated that an inflammatory-like response occurs in the uterus upon estrogen treatment. The goal of this study was to elucidate if a correlation exists between the presence of granulocytes, which include neutrophils, eosinophils, and basophils, in the rat uterus and the appearance of remodeling events that occurs, following treatment with the ovarian steroid hormone, estrogen. I was also interested in learning if granulocytopenia altered the ability of the uterus to produce chemokine signals that are thought to attract granulocytes to the uterus during the remodeling phase of the uterine growth response to estrogen. Therefore, in this study I utilized a rodent model in which a state of granulocytopenia was induced. The rats were then treated with a physiological dose of estrogen, and transmission electron microscopy (TEM) technology was used to assess matrix density in ultra-thin slices of harvested uteri from experimental rats. This investigation also employed immunohistochemistry and fluorescence microscopy to examine the presence of granulocytes in the endometrial compartment, as well as Western blots and gene expression assays to determine the effect of granulocytopenia on the chemokines that attract these leukocytes. Overall, based on the TEM data, granulocytes were found to be necessary for matrix turnover events; however, based on these same data, it is apparent that other components of the endometrium, probably molecular inflammatory mediators and chemokines, are also critical to this process. Immunohistochemistry demonstrated that granulocytes are indeed depleted in uterine tissue twenty-two hours after anti-PMN antiserum administration, even upon estrogen stimulation, as compared to the controls. Finally, in general, as expected, a state of granulocytopenia has no significant impact on uterine chemokine expression. While this study more closely examined this inflammatory-like response by analyzing the structure of the extracellular matrix in the presence and absence of granulocytes, further investigation of this process is necessary to establish a cause and effect relationship between tissue remodeling and the presence of granulocytes in the uterus.
Language: English
Format: Degree Work