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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Significantly increased lymphatic microvessel density in women with endometriosis has been described in the endometrium during the proliferative phase.
“Furthermore, significantly increased lymphatic microvessel density in women with endometriosis has been described in the endometrium during the proliferative phase, 94”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [94]
Cites
Rw, N., Hertig, A. T., & Rock, J. A. (1950) · Fertility and Sterility · doi:10.1016/s0015-0282(16)30062-0 · Cited by 2,854 · see citing works
Angiosarcomas Express Mixed Endothelial Phenotypes of Blood and Lymphatic Capillaries
Breiteneder-Geleff, S., Soleiman, A., Kowalski, H., Horvat, R., Amann, G., Kriehuber, E., Diem, K., Weninger, W., Tschachler, E., Alitalo, K. K., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65285-6 · Cited by 1,088 · see citing works
Expression of hypoxia-inducible factor 1? in brain tumors
Zagzag, D., Zhong, H., Scalzitti, J. M., Laughner, E., Simons, J. W., & Semenza, G. L. (2000) · Cancer · doi:10.1002/1097-0142(20000601)88:11 · Cited by 603 · see citing works
Vascular endothelial growth factor (VEGF) in endometriosis
Donnez, J., Smoes, P., Gillerot, S., Casanas-Roux, F., & Nisolle, M. (1998) · Human Reproduction · doi:10.1093/humrep/13.6.1686 · Cited by 531 · see citing works
Endometrial leukocytes and menstruation
Salamonsen, L. A. (2000) · Human Reproduction Update · doi:10.1093/humupd/6.1.16 · Cited by 295 · see citing works
Macrophage expression in endometrium of women with and without endometriosis
Berbic, M., Schulke, L., Markham, R., Tokushige, N., Russell, P. J., & Fraser, I. S. (2008) · Human Reproduction · doi:10.1093/humrep/den393 · Cited by 204 · see citing works
Self-citationБурлев, В. А., Volkov, N. I., Pavlovitch, S. V., Lets, N., Larsson, A. O., & Olovsson, M. (2006) · Reproduction · doi:10.1530/rep.1.01110 · Cited by 192 · see citing works
Endometrial Anomalies in Women with Endometriosis
Sharpe-Timms, K. L. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03797.x · Cited by 187 · see citing works
Dendritic cell populations in the eutopic and ectopic endometrium of women with endometriosis
Schulke, L., Berbic, M., Manconi, F., Tokushige, N., Markham, R., & Fraser, I. S. (2009) · Human Reproduction · doi:10.1093/humrep/dep071 · Cited by 176 · see citing works
Self-citationGombos, Z., Xu, X., Chu, C., Zhang, P. J., & Ács, G. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1238 · Cited by 176 · see citing works
The Role of Endometrium in Endometriosis
Ulukuş, M., Çakmak, H., & Arici, A. M. (2006) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2006.07.005 · Cited by 171 · see citing works
INTESTINAL ADENOMAS OF ENDOMETRIAL TYPE
SAMPSON, J. A. (1922) · Archives of Surgery · doi:10.1001/archsurg.1922.01110140003001 · Cited by 165 · see citing works
Differential macrophage infiltration in early and advanced endometriosis and adjacent peritoneum
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., & Ishimaru, T. (2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.07.037 · Cited by 161 · see citing works
Berbic, M., Hey‐Cunningham, A. J., Ng, C. H. M., Tokushige, N., Ganewatta, S. P., Markham, R., Russell, P. J., & Fraser, I. S. (2010) · Human Reproduction · doi:10.1093/humrep/deq020 · Cited by 158 · see citing works
Self-citationJavert, C. T. (1949) · Cancer · doi:10.1002/1097-0142(194905)2:3 · Cited by 150 · see citing works
CD83: an update on functions and prospects of the maturation marker of dendritic cells
Prechtel, A. T., & Steinkasserer, A. (2007) · Archives of Dermatological Research · doi:10.1007/s00403-007-0743-z · Cited by 147 · see citing works
Gilabert–Estellés, J., Ramón, L., España, F., Gilabert, J., Vila, V., Regañón, E., Castelló, R., Chirivella, M., & Estellés, A. (2007) · Human Reproduction · doi:10.1093/humrep/dem149 · Cited by 126 · see citing works
Vascular Proliferation Is Important for Clinical Progress of Endometrial Cancer
Stefansson, I. M., Salvesen, H. B., & Akslen, L. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1163 · Cited by 126 · see citing works
Is endometriosis an endometrial disease?
Vinatier, D., Cosson, M., & Dufour, P. (2000) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(99)00263-8 · Cited by 115 · see citing works
Vascular endothelial growth factor A and C gene expression in endometriosis
Takehara, M., Ueda, M., Yamashita, Y., Terai, Y., Hung, Y., & Ueki, M. (2004) · Human Pathology · doi:10.1016/j.humpath.2004.07.020 · Cited by 110 · see citing works
Braun, D. P., Ding, J., & Dmowski, W. P. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03318-6 · Cited by 105 · see citing works
Tan, X., Lang, J., Liu, D., Shen, K., Leng, J., & Zhu, L. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(02)03187-4 · Cited by 100 · see citing works
Histologic study of endometriosis and examination of lymphatic drainage in and from the uterus
Ueki, M. (1991) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(91)90252-m · Cited by 82 · see citing works
Khan, K. N., Masuzaki, H., Fujishita, A., Kitajima, M., Sekine, I., & Ishimaru, T. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04535-1 · Cited by 78 · see citing works
Mechsner, S., Weichbrodt, M., Riedlinger, W. F. J., Bartley, J., Kaufmann, A. M., Schneider, A., & Kohler, C. (2008) · Human Reproduction · doi:10.1093/humrep/den259 · Cited by 69 · see citing works
Lymphangiogensis of normal endometrium and endometrial adenocarcinoma
Donoghue, J. F., Lederman, F. L., Susil, B. J., & Rogers, P. A. W. (2007) · Human Reproduction · doi:10.1093/humrep/dem037 · Cited by 65 · see citing works
Angiopoietin-1, angiopoietin-2 and Tie-2 expression in eutopic endometrium in advanced endometriosis
Hur, S. E. (2006) · Molecular Human Reproduction · doi:10.1093/molehr/gal049 · Cited by 58 · see citing works
Longatto‐Filho, A., Pinheiro, C. M., PEREIRA, S., Etlinger, D., Moreira, M. A. R., Jubé, L. F., QUEIROZ, G., Baltazar, F., & Schmitt, F. C. (2007) · Gynecologic Oncology · doi:10.1016/j.ygyno.2007.05.029 · Cited by 52 · see citing works
Endometrial leukocyte subpopulations in women with endometriosis
Klentzeris, L. D., Bulmer, J. N., Liu, D. T. Y., & Morrison, L. (1995) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0301-2115(95)02222-s · Cited by 46 · see citing works
Matsuzaki, S., Canis, M., Darcha, C., Dechelotte, P., Pouly, J. L., & Bruhat, M. A. (1998) · Gynecologic and Obstetric Investigation · doi:10.1159/000010013 · Cited by 43 · see citing works
Superficial lymphatics in the functional zone of normal human endometrium
Blackwell, P. M., & Fraser, I. S. (1981) · Microvascular Research · doi:10.1016/0026-2862(81)90027-3 · Cited by 33 · see citing works
Self-citationInflammatory changes of the endometrium in patients with minimal-to-moderate endometriosis
Leiva, M. C., Hasty, L. A., & Lyttle, C. R. (1994) · Fertility and Sterility · doi:10.1016/s0015-0282(16)57059-9 · Cited by 33 · see citing works
Lymphatic vessel density as a prognostic indicator for patients with stage I cervical carcinoma
Gao, P., Zhou, G., Yin, G., Liu, Y., Liu, Z., Zhang, J., & Hao, C. (2006) · Human Pathology · doi:10.1016/j.humpath.2006.01.025 · Cited by 31 · see citing works
Increased expression of endoglin in the eutopic endometrium of women with endometriosis
Kim, S. H., Choi, Y. M., Chae, H. D., Kim, K. R., Kim, C. H., & Kang, B. M. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)02733-9 · Cited by 29 · see citing works
A Rare Case of Rectovaginal Endometriosis with Lymph Node Involvement
Thomakos, N., Rodolakis, A., Vlachos, G. D., Papaspirou, I., Markaki, S. P., & Antsaklis, A. J. (2006) · Gynecologic and Obstetric Investigation · doi:10.1159/000091998 · Cited by 25 · see citing works
Bilateral ureteral endometriosis with end-stage renal failure
Mourin-Jouret, A., Squifflet, J. P., Cosyns, J. P., Pirson, Y., & Alexandre, G. P. (1987) · Urology · doi:10.1016/0090-4295(87)90075-6 · Cited by 17 · see citing works
Бурлев, В. А., Ilyasova, N. A., & Dubinskaya, E. D. (2005) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-005-0391-2 · Cited by 16 · see citing works
Lu, X.-E., Ning, W., Dong, M.-Y., Liu, A., Jin, F., & Huang, H. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.12.083 · Cited by 16 · see citing works
Microanatomy and function of the eutopic endometrium in women with endometriosis
Al‐Jefout, M., Tokushige, N., Hey‐Cunningham, A. J., Manconi, F., Ng, C. H. M., Schulke, L., Berbic, M., Markham, R., & Is, F. (2008) · Expert Review of Obstetrics & Gynecology · doi:10.1586/17474108.4.1.61 · Cited by 15 · see citing works
Self-citationGescher, D. M., Siggelkow, W., Meyhöfer-Malik, A., & Malik, E. (2004) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-004-0688-9 · Cited by 13 · see citing works
Anginogenesis of eutopic and ectopic endometria in endometriosis
Liu, Y., Liqun, L., & Gui-jin, Z. (2003) · Current Medical Science · doi:10.1007/bf02859954 · Cited by 7 · see citing works
Rösner, N., & Böger, A. (1979) · European Urology · doi:10.1159/000473137 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lymphatic Vessel Network Structure and Physiology
Breslin, J. W., Yang, Y., Scallan, J. P., Sweat, R. S., Adderley, S., & Murfee, W. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c180015 · Cited by 402 · see citing works
Rogers, P. A. W., D’Hooghe, T. M., Fazleabas, A., Giudice, L. C., Montgomery, G. W., Petraglia, F., & Taylor, R. N. (2013) · Reproductive Sciences · doi:10.1177/1933719113477495 · Cited by 154 · see citing works
The eutopic endometrium in endometriosis: are the changes of clinical significance?
Brosens, I. A., Brosens, J. J., & Benagiano, G. (2012) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2012.01.022 · Cited by 124 · see citing works
The Role of the Lymphatic System in Endometriosis: A Comprehensive Review of the Literature1
Jerman, L. F., & Hey-Cunningham, A. J. (2015) · Biology of Reproduction · doi:10.1095/biolreprod.114.124313 · Cited by 122 · see citing works
Self-citationLymphatic Vessel Network Structure and Physiology
Breslin, J. W., Yang, Y., Scallan, J. P., Sweat, R. S., Adderley, S., & Murfee, W. L. (2019) · Comprehensive physiology · doi:10.1002/j.2040-4603.2019.tb00063.x · Cited by 71 · see citing works
Angiogenesis lymphangiogenesis and neurogenesis in endometriosis
Hey‐Cunningham, A. J. (2013) · Frontiers in Bioscience-Elite · doi:10.2741/e682 · Cited by 68 · see citing works
Self-citationWattanayingcharoenchai, R., Rattanasiri, S., Charakorn, C., Attia, J., & Thakkinstian, A. (2021) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.16366 · Cited by 58 · see citing works
Hey‐Cunningham, A. J., Markham, R., Fraser, I. S., & Berbic, M. (2013) · Reproductive Sciences · doi:10.1177/1933719113485299 · Cited by 22 · see citing works
Self-citationUltrastructural Features of Eutopic Endometrium in a Rat Model of Endometriosis
Elgamal, D. A., Othman, E. R., & Ahmed, S. (2015) · Journal of Microscopy and Ultrastructure · doi:10.1016/j.jmau.2015.10.002 · Cited by 20 · see citing works
Sheveleva, T., Bejenar, V. F., Komlichenko, E. V., Dedul, A. G., & Викторович, М. А. (2016) · Gynecological Endocrinology · doi:10.1080/09513590.2016.1232789 · Cited by 19 · see citing works
The endometrial lymphatic vasculature: Function and dysfunction
Girling, J. E., & Rogers, P. A. W. (2012) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-012-9224-6 · Cited by 11 · see citing works
Endometrioma: From Pathogenesis to Clinical Management
Luisi, S. V., Renner, S. P., & Santulli, P. (2013) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.5000163 · Cited by 5 · see citing works
Comparative analysis of eutopic endometrium from women with and without endometriosis
Adamyan, L. V., Aznaurova, Y. B., & Osipova, A. A. (2018) · Russian Journal of Human Reproduction · doi:10.17116/repro201824310 · Cited by 1 · see citing works
FACTORS OF ENDOMETRIAL RECEPTIVITY DOWN-REGULATION IN GENITAL ENDOMETRIOSIS
Marinkin, I. O., Aidagulova, S. V., Кулешов, В. М., & Timofeeva, Y. S. (2020) · Репродуктивная медицина · doi:10.37800/rm2020-1-13 · Cited by 1 · see citing works
Ersoy, B. (2015) · The Sydney eScholarship Repository (The University of Sydney) · Cited by 1 · see citing works
Roles of regulatory T cells in endometriosis-associated infertility
Riaz, A. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University) · Cited by 1 · see citing works
- Authors
- Hey-Cunningham, A. J., Ng, F. W., Busard, M. P. H., Berbic, M., Manconi, F., Young, L., Zevallos, H. B.-V., Russell, P., Markham, R., & Fraser, I. S.
- Affiliations
- Department of Obstetrics, Gynaecology and Neonatology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney - Australia
- The University of Sydney (AU)
- Venue
- Journal of Endometriosis
- Publisher
- SAGE Publications
- Published
- 2010-10
- Volume
- 2
- Issue
- 4
- Pages
- 197-204
- ISSN
- 2035-9969 (ISSN-L)
- 2036-282X
- OpenAlex
- W4233460300
- Cited by
- 16
- References
- 42
- Citations by year
- 2020: 2 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 2
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endometriosis and Pelvic Pain Disorders (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometriosis, uterine blood vessels, blood vessel density, menstrual cycle, CD105, angiogenesis, retrograde menstruation, endometrial shedding, endometrium, lymphatic spread
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
