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.

Lymphatic Vessel Network Structure and Physiology

“…Similar findings were also reported in sheep, with subsequent draining to subserosal lymphatics and the lumbar lymph nodes (1178). In serial sections of human endometrium, lymphatic networks were found in both the functionalis and basalis regions (99) layers (434). The lymphatics in the basalis region are in close contact with the spiral arteries, which are known to have a key role in menstruation and placentation (99, 276, 1090, 1107).…”

Ultrastructural Features of Eutopic Endometrium in a Rat Model of Endometriosis

“…The existing controversies concerning the pathophysiology of endometriosis and its influence on pregnancy and vice versa demonstrate the need for research in laboratory animals [ 9 ]. Recent studies was done on the structural and biochemical changes [ 10 ], endometrial nerve fiber [ 11 ], endometrial angiogenesis [ 12 ] and endometrial receptivity in endometriosis [ 13 ]. Previous studies made morphological and functional comparison between the ectopic and eutopic endometrium in pregnant rats [ 8 ].…”

Innovative approach in assessing the role of neurogenesis, angiogenesis, and lymphangiogenesis in the pathogenesis of external genital endometriosis

“…These data suggest a higher angiogenic potential of endometrial tissue of women with endometriosis and expected to increase the ability to ectopic endometrial invasion and survival in the abdominal cavity [34].…”