Uterine Lymphatic and Blood Micro-Vessels in Women with Endometriosis through the Menstrual Cycle

Abstract

Purpose Endometriosis is a common disease, associated with persistent and severe symptoms including infertility and pain, however, pathogenesis remains poorly understood. It has been hypothesized that fragments of viable endometrial tissue shed at menstruation reach the peritoneal cavity and other distant sites by retrograde menstruation and dissemination into the lymphatic system. In this study, uterine lymphatic and blood micro-vessel populations were compared in women with and without endometriosis during the menstrual cycle. Methods Paraffin-embedded hysterectomy specimens from premenopausal women with histologically normal endometrium (37 control and 42 endometriosis) were obtained. Immunohistochemical staining was performed with antibodies for D2–40 (lymphatic endothelium), CD31 (pan-endothelial marker), and endoglin (activated endothelial cells in angiogenesis). Lymphatic (LVD) and blood (BVD) micro-vessel density were quantified with an automated cellular imaging system using color and morphometric properties to identify micro-vessels. Results Subtle but significant differences in uterine BVD and LVD were detected in endometriosis. LVD was significantly increased in basal layer endometrium of endometriosis patients during the proliferative phase (mean ± SD = 54.3 ± 20.1 vs. 41.4 ± 9.9, p = 0.025). Endoglin-positive BVD was increased in the subepithelial region of endometrium in endometriosis during the secretory phase (19.3 ± 16.6 vs. 6.4 ± 8.2, p = 0.038). Conclusions This report for the first time demonstrates that endometrial LVD is altered in women with endometriosis and supports changes in BVD in these women. These alterations are likely to contribute to pathogenesis of endometriosis, through lymphatic spread and increased angiogenic potential of shed endometrial fragments.