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Objective: To examine total ezrin expression (ezrin and phospho-ezrin) through the normal endometrial cycle and to correlate ezrin activation and localization with cytologic changes. Design: Experimental laboratory study. Setting: University medical centers. Patient(s): Reproductive-age women. Intervention(s): A total of 36 samples of normal early, mid-, and late proliferative- and secretory-phase endometrium were studied for immunoreactive total ezrin (ir-T-ezrin) and phospho-ezrin (ir-p-ezrin) expression by histology, immunohistochemistry, and Western blotting. Main Outcome Measure(s): Total ezrin and phospho-ezrin expressions through the normal endometrial cycle. Result(s): Throughout the cycle ir-T-ezrin is present in the epithelium. The intensity and localization of both ir-ezrin and ir-p-ezrin vary greatly throughout the cycle. The main findings include the following: lateral localization of ir-ezrin/ir-p-ezrin in association with membrane specializations; dense staining around secretory vacuoles (secretory phase); dense staining of the apical surfaces, including microvilli and pinopodes of epithelial cells, especially during the mid- to late secretory phases; and the presence of ezrin in the glandular secretions. Immunoreactive total ezrin and ir-p-ezrin were not expressed by stromal fibroblasts. Conclusion(s): Ezrin is a prominent protein in the cycling endometrium. The most striking findings were the gravitation of ir-ezrin/ir-p-ezrin to the periphery of secretory vacuoles, localization on apical surfaces of the luminal epithelium, dense ezrin staining in secretory-phase epithelial cell plumes, and the presence of ir-ezrin/ir-p-ezrin in secretory-phase luminal secretions. These findings may have functional implications, especially for implantation biology. [ABSTRACT FROM AUTHOR]