Progressive rise in the expression of interleukin-6 in human endometrium during menstrual cycle is initiated during the implantation window

Abstract

In order to be prepared for implantation, human endometrium undergoes a predictable series of proliferative and secretory changes. Cytokines play an important role in regulation of these changes. Therefore, in this study, we immunolocalized the cytokine, interleukin-6 (IL-6), its receptor and the signal transducer gp130 in human endometrium throughout the menstrual cycle. During the entire menstrual cycle, the IL-6 receptor and gp130 were found primarily in the endometrial glands and to a lesser extent in the stroma. The immunoreactivity of these proteins did not change in endometrial cells during the entire menstrual cycle with an exception of reduced immunoreactivity of gp130 in endometrial glands during menstrual phase. Immunostaining showed that immunoreactive IL-6 was weakly expressed in human endometrium during the proliferative phase. Strong immunoreactivity for IL-6 appeared in endometrium during the putative 'implantation window'. Expression was by far most pronounced both in the glandular and surface epithelial cells. The amount of immunoreactive IL-6 in the epithelium progressively increased during the secretory/menstrual phases. During the late secretory phase, only stromal cells in the upper functionalis exhibited immunoreactivity for IL-6. Western blot analysis corroborated the immunohistochemical data. Human endometrial IL-6 consisted of a protein with an apparent mobility of 26 kDa. The immunoreactive band of IL-6 was weak in the proliferative phase. The expression of this protein increased progressively during the secretory/menstrual phases. The findings show a cell-specific pattern of distribution for immunoreactive IL-6 in human endometrium. The menstrual cycle-dependent expression of IL-6 suggests that this cytokine may play a role in changes in endometrium that prepare this tissue for implantation and menstrual shedding.