Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients

Abstract

Objective: To evaluate nuclear factor kappaB (NF-kB) activation and NF-kB–p65 subunit activation, immunolocalization, and expression in the endometrium of healthy women and endometriosis patients throughout the menstrual cycle. Design: Prospective observational study. Setting: Affiliated hospital and university research laboratory. Patient(s): Twenty-four healthy women and 24 endometriosis patients. Intervention(s): Menstrual, proliferative, and secretory endometrial biopsies. Main Outcome Measure(s): Assessment of NF-kB and p65 activation by protein-DNA binding assays and p65 localization and expression by immunohistochemistry. Result(s): Total NF-kB–DNA binding was constitutive and variable in human endometrium accross the menstrual cycle. Healthy women (physiologic conditions) showed higher p65-DNA binding in proliferative than in menstrual and secretory endometrium. Conversely, in endometriosis patients, p65-DNA binding was higher in proliferative and secretory endometrium than in menstrual endometrium. Endometrial epithelial cells showed higher p65 expression level score than endometrial stromal cells. Conclusion(s): NF-kB activity is constitutive, physiologic, and variable in human endometrium. The physiologic cyclic p65 activation pattern was altered in endometriosis patients, showing no cyclic variation between the proliferative and secretory phase of the menstrual cycle. The absence of decreased p65 activity in secretory endometrium from endometriosis patients is concurrent with progesterone resistance and could participate in endometrial biologic alterations during the implantation window in endometriosis patients.