Expression of Cytoskeletal-Linking ERM (Ezrin, Radixin and Moesin) Proteins in Human Endometrium

ERM (ezrin, radixin and moesin) protein family is composed of cytoskeletal-linking proteins playing a role in cell adhesion, migration and organization of cell surface structures such as microvilli formation. We hypothesized that ezrin, radixin and moesin are present and differentially expressed in normal endometrium and they play a role in organizing cell surface structures such as microvilli and pinopodes. Endometrial tissues from reproductive age women (mean age 33±13 years) were obtained from endometrial biopsies and human uteri after hysterectomy conducted for benign diseases other than endometrial disease following institutional review board approval. A total of thirty endometrial samples from different phases of normal endometrium were studied. Early proliferative (n = 5), mid proliferative (n = 5), late proliferative (n = 5), early secretory (n = 5), mid secretory (n = 5) and late secretory phase (n = 5) endometrial samples were analyzed for immunoreactive (ir) ezrin, radixin and moesin by immunohistochemical analysis. Differences in HSCORE values among different phases of normal endometrium were analyzed by using one-way ANOVA test. Differences in HSCORE values comparing glandular cells with stromal cells from the same endometrial phase were analyzed using Student's t-test. A p value of <0.05 was considered statistically significant. Ir-ezrin and ir-radixin were present but ir-moesin was absent through the endometrial cycle. The intensity and localization of both ir-ezrin and ir-radixin vary greatly throughout the cycle. Ir-ezrin and ir-radixin were present in luminal epithelium, glandular and stromal cells through the normal endometrium. The main findings include: lateral localization of ir-ezrin/ir-radixin 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 and radixin in the glandular secretions. During the mid secretory phase, pinopodes, which are sponge-like smooth membrane projections that are present around the presumed time of blastocyst implantation, were seen to thicken and extend to the globular luminal surface. Ir-ezrin and ir-radixin were clearly expressed in luminal epithelial pinopodes. Expression of ezrin and radixin on apical surfaces of luminal and glandular epithelium, pinopodes, microvilli and dense radixin staining of stromal cells during the mid and late secretory phases are all novel findings. These findings may have functional implications, especially for implantation biology.