A Novel Pilot Study of Endometrial Stromal Cells and Immune Cell Populations in Sentinel Uterine-Draining Lymph Nodes During the Menstrual Cycle and in Endometriosis

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Endometrial stromal cells and immune cells were detected in uterine-draining lymph nodes, with their numbers fluctuating during the menstrual cycle and showing altered patterns in endometriosis.

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This pilot study examined paraffin-embedded sentinel uterine-draining lymph nodes (obturator LNs) from women with and without endometriosis, using immunohistochemistry to identify CD10+ endometrial stromal cells and multiple immune cell populations across the menstrual cycle. CD10+ endometrial stromal cells were present throughout the menstrual cycle with a peak during menstruation, and menstrual inflammation was accompanied by increased T cells, regulatory T cells (Foxp3+), dendritic cells (DC-Sign+), macrophages (CD68+), B cells (CD20+/CD79+), and plasma cells. In women with endometriosis, CD10+ stromal cells were further increased, while several immune populations (including CD3+, CD4+, DC-Lamp+, Foxp3+ cells, and plasma cells) were reduced. The study explicitly relies on a small, cancer-surgery-derived LN sample with limited power and observational cross-sectional comparisons. This paper is centrally about endometriosis — it evaluates altered endometrial stromal cell and immune cell dynamics in sentinel uterine-draining lymph nodes during the menstrual cycle and in endometriosis.

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Abstract

Recent studies suggest that changes in certain uterine immune cell populations in endometrium of women with endometriosis are likely to precede changes at ectopic sites. This preliminary study is a first look into the function of uterine-draining lymph nodes (LNs) during the menstrual cycle and in the presence of endometriosis. Paraffin-embedded obturator LNs were obtained from women with (n = 7, mean age 44.3) and without (n = 9, mean age 38.4) endometriosis, who had undergone hysterectomy for cervical or ovarian cancer and in whom LN involvement was not detected. Immunohistochemical staining for endometrial stromal cells and a range of immune cell populations was performed. The CD10+ endometrial stromal cells were detected in uterine-draining LNs throughout the menstrual cycle with numbers peaking during menstruation. The inflammatory process of menstruation was also associated with increased numbers of CD3+, CD4+, Foxp3+, DC-Sign+, CD68+, CD20+, CD79+, and plasma cells. In endometriosis, CD10+ endometrial stromal cells were further increased in numbers, but CD3+, CD4+, DC-Lamp+, FoxP3+, and plasma cells were reduced. This study indicates that efficient immunological responses may be required to contain shed endometrial fragments within the draining uterine LNs thus preventing their further dissemination with establishment of ectopic lesions at distant sites.
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Abstract

Recent studies suggest that changes in certain uterine immune cell populations in endometrium of women with endometriosis are likely to precede changes at ectopic sites. This preliminary study is a first look into the function of uterine-draining lymph nodes (LNs) during the menstrual cycle and in the presence of endometriosis. Paraffin-embedded obturator LNs were obtained from women with (n = 7, mean age 44.3) and without (n = 9, mean age 38.4) endometriosis, who had undergone hysterectomy for cervical or ovarian cancer and in whom LN involvement was not detected. Immunohistochemical staining for endometrial stromal cells and a range of immune cell populations was performed. The CD10+ endometrial stromal cells were detected in uterine-draining LNs throughout the menstrual cycle with numbers peaking during menstruation. The inflammatory process of menstruation was also associated with increased numbers of CD3+, CD4+, Foxp3+, DC-Sign+, CD68+, CD20+, CD79+, and plasma cells. In endometriosis, CD10+ endometrial stromal cells were further increased in numbers, but CD3+, CD4+, DC-Lamp+, FoxP3+, and plasma cells were reduced. This study indicates that efficient immunological responses may be required to contain shed endometrial fragments within the draining uterine LNs thus preventing their further dissemination with establishment of ectopic lesions at distant sites. Similar content being viewed by others

References

Salamonsen LA, Woolley DE. Menstruation: induction by matrix metalloproteinases and inflammatory cells. J Reprod Immunol. 1999;44(1–2):1–27. Bulmer JN, Longfellow M, Ritson A. Leukocytes and resident blood cells in endometrium. Ann N Y Acad Sci. 1991;622:57–68. Klentzeris LD, Bulmer JN, Warren A, et al. Endometrial lymphoid tissue in the timed endometrial biopsy: morphometric and immuno-histochemical aspects. Am J Obstet Gynecol. 1992;167(3):667–674. Salamonsen LA, Lathbury LJ. Endometrial leukocytes and menstruation. Hum Reprod Update. 2000;6(1):16–27. Tanaka H, Sato H, Miura H, et al. Can we omit para-aorta lymph node dissection in endometrial cancer?. Jpn J Clin Oncol. 2006;36(9):578–581. Netter FH. A compilation of paintings on the normal and pathologic anatomy of the reproductive system. In: Oppenheimer E, ed. The CIBA Collection of Medical Illustrations. New York, NY: Ciba Pharmaceutical Company; 1965:2. Finn CA. Implantation, menstruation and inflammation. Biol Rev Camb Philos Soc. 1986;61(4):313–328. Salamonsen LA, Zhang J, Brasted M. Leukocyte networks and human endometrial remodelling. J Reprod Immunol. 2002;57(1–2):95–108. Podgaec S, Abrao MS, Dias JA Jr, Rizzo LV, de Oliveira RM, Baracat EC. Endometriosis: an inflammatory disease with a Th2 immune response component. Hum Reprod. 2007;22(5):1373–1379. Schulke L, Berbic M, Manconi F, Tokushige N, Markham R, Fraser IS. Dendritic cell populations in the eutopic and ectopic endometrium of women with endometriosis. Hum Reprod. 2009;24(7):1695–1703. Bulmer JN, Jones RK, Searle RF. Intraepithelial leukocytes in endometriosis and adenomyosis: comparison of eutopic and ectopic endometrium with normal endometrium. Hum Reprod. 1998;13(10):2910–2915. Akoum A, Metz CN, Al-Akoum M, Kats R. Macrophage migration inhibitory factor expression in the intrauterine endometrium of women with endometriosis varies with disease stage, infertility status, and pelvic pain. Fertil Steril. 2006;85(5):1379–1385. Berbic M, Schulke L, Markham R, Tokushige N, Russell P, Fraser IS. Macrophage expression in endometrium of women with and without endometriosis. Hum Reprod. 2009;24(2):325–332. Berbic M, Hey-Cunningham AJ, Ng C, et al. The role of Foxp3+ regulatory T-cells in endometriosis, a potential controlling mechanism for a complex, chronic immunological condition. Hum Reprod. 2010;25(4):900–907. Beliard A, Donnez J, Nisolle M, Foidart JM. Localization of laminin, fibronectin, E-cadherin, and integrins in endometrium and endometriosis. Fertil Steril. 1997;67(2):266–272. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13(6):1689–1690. Hull ML, Charnock-Jones DS, Chan CL, et al. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab. 2003;88(6):2889–2899. Javert CT. Pathogenesis of endometriosis based on endometrial homeoplasia, direct extension, exfoliation and implantation, lymphatic and hematogenous metastasis, including five case reports of endometrial tissue in pelvic lymph nodes. Cancer. 1949;2(3):399–410. Halban J. Hysteroadenosis metastatica. Wien klin Woschensch. 1924;37:1205–1206. Sampson JA. Intestinal adenomas of endometrial type: their importance and their relation to ovarian hematomas of endometrial type (perforating hemorrhagic cysts of the ovary). Arch Surg. 1922;5(2):217–280. Mechsner S, Weichbrodt M, Riedlinger WF, Kaufmann AM, Schneider A, Köhler C. Immunohistochemical evaluation of endometriotic lesions and disseminated endometriosis-like cells in incidental lymph nodes of patients with endometriosis. Fertil Steril. 2010;94(2):457–463. Gong Y, Tempfer CB. Regional lymphatic spread in women with pelvic endometriosis. Med Hypotheses. 2011;76(4):560–563. Zhang J, Salamonsen LA. In vivo evidence for active matrix metalloproteinases in human endometrium supports their role in tissue breakdown at menstruation. J Clin Endocrinol Metab. 2002;87(5):2346–2351. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–252. Khan KN, Kitajima M, Hiraki K, et al.. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil Steril. 2010;94(7):2860–2863. e3. White HD, Crassi KM, Givan AL, et al. CD3+ CD8+ CTL activity within the human female reproductive tract: influence of stage of the menstrual cycle and menopause. J Immunol. 1997;158(6):3017–3027. McCluggage WG, Sumathi VP, Maxwell P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histo-pathology. 2001;39(3):273–278. McIntosh GG, Lodge AJ, Watson P, et al. NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue. Am J Pathol. 1999;154(1):77–82. Dogan A, Bagdi E, Munson P, Isaacson PG. CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. Am J Surg Pathol. 2000;24(6):846–852. Malik S, Day K, Perrault I, Charnock-Jones DS, Smith SK. Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-α in menstrual endometrium and effluent in women with menorrhagia. Hum Reprod. 2006;21(8):2158–2166. Schulke L, Manconi F, Markham R, Fraser IS. Endometrial dendritic cell populations during the normal menstrual cycle. Hum Reprod. 2008;23(7):1574–1580. Mechsner S, Weichbrodt M, Riedlinger WF, et al. Estrogen and progestogen receptor positive endometriotic lesions and disseminated cells in pelvic sentinel lymph nodes of patients with deep infiltrating rectovaginal endometriosis: a pilot study. Hum Reprod. 2008;23(10):2202–2209. Zhou T, Chen Y, Hao L, Zhang Y. DC-SIGN and immunoregulation. Cell Mol Immunol. 2006;3(4):279–283. Smith S, Abel M, Kelly R, Baird DT. Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding. Br J Obstet Gynaecol. 1981;88(4):434–442. Sawicki G, Salas E, Murat J, et al. Release of gelatinase A during platelet activation mediates aggregation. Nature. 1997;386(6625):616–619. Gebel HM, Braun DP, Tambur A, Frame D, Rana N, Dmowski WP. Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis. Fertil Steril. 1998;69(6):1042–1047. Dmowski WP, Gebel H, Braun DP. Decreased apoptosis and sensitivity to macrophage mediated cytolysis of endometrial cells in endometriosis. Hum Reprod Update. 1998;4(5):696–701. Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O, Tesone M, Rumi LS. Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis. Fertil Steril. 2000;74(4):760–766. Hey-Cunningham AJ, Ng FW, Busard MPH, et al. Uterine lymphatic and blood micro-vessels in women with endometriosis throughout the menstrual cycle. J Endo. 2010;2(4):197–204. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14:422–469. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799. Mourin-Jouret A, Squifflet JP, Cosyns JP, Pirson Y, Alexandre GP. Bilateral ureteral endometriosis with end-stage renal failure. Urology. 1987;29(3):302–306. Wu DC, Hirschowitz S, Natarajan S. Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall. Arch Pathol Lab Med. 2005;129(5):e117–e120. Burke TW, Levenback C, Tornos C, Morris M, Wharton JT, Gershenson DM. Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer: results of a pilot study. Gynecol Oncol. 1996;62(2):169–173. Mariani A, Webb MJ, Keeney GL, Podratz KC. Routes of lymphatic spread: a study of 112 consecutive patients with endometrial cancer. Gynecol Oncol. 2001;81(1):100–104. O’Boyle JD, Coleman RL, Bernstein SG, Lifshitz S, Muller CY, Miller DS. Intraoperative lymphatic mapping in cervix cancer patients undergoing radical hysterectomy: a pilot study. Gynecol Oncol. 2000;79(2):238–243. Trbojević J, Nešić D, Laušević Ž, Brajušković G, Miljana O, Biljana S. Histological characteristics of healthy animal peritoneum. Acta Vet (Beogr). 2006;56(5–6):405–412. Hey-Cunningham AJ, Berbic M, Ng C, Markham R, Fraser I. Lymphatic vessels in peritoneal endometriotic lesions. J Endo. 2011;3(2):59–66. Chiang CM, Hill JA. Localization of T cells, interferon-gamma and HLA-DR in eutopic and ectopic human endometrium. Gynecol Obstet Invest. 1997;43(4):245–250. Jones RK, Bulmer JN, Searle RF. Phenotypic and functional studies of leukocytes in human endometrium and endometriosis. Hum Reprod Update. 1998;4(5):702–709. Dmowski WP, Braun DP. Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):245–263. Poropatich C, Rojas M, Silverberg SG. Polymorphonuclear leukocytes in the endometrium during the normal menstrual cycle. Int J Gynecol Pathol. 1987;6(3):230–234. Noël JC, Chapron C, Fayt I, Anaf V. Lymph node involvement and lymphovascular invasion in deep infiltrating rectosigmoid endometriosis. Fertil Steril. 2008;89(5):1069–1072. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Berbic, M., Ng, C.H.M., Black, K. et al. A Novel Pilot Study of Endometrial Stromal Cells and Immune Cell Populations in Sentinel Uterine-Draining Lymph Nodes During the Menstrual Cycle and in Endometriosis. Reprod. Sci. 20, 1339–1348 (2013). https://doi.org/10.1177/1933719113485298 Published: Issue date: DOI: https://doi.org/10.1177/1933719113485298

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endometriosis

MeSH descriptors

Endometriosis Endometrium Lymph Nodes Menstrual Cycle Plasma Cells Stromal Cells Adult Biomarkers Biomarkers Case-Control Studies Disease Progression Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Humans Immunohistochemistry Lymph Nodes

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