Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis: The Possible Immune Privilege of Ectopic Endometrium

The Fas/Fas-Ligand system is an important mediator of apoptosis. We analyzed their expression in tissue specimens obtained from 33 women with severe endometriosis and 18 women without endometriosis. Immunostaining for Fas-Ligand in the eutopic endometrium was stronger in the epithelial cells of secretory phase, while the epithelial cells of endometriotic lesions showed a significantly stronger staining for Fas-Ligand independently from the menstrual phase (P < 0.01). Immunostaining for Fas in the eutopic endometrium showed a reduced staining during the proliferative phase, whereas it was strong in the secretory phase. The epithelial cells of the ectopic endometrium showed a reduced staining for Fas independently from the menstrual phase with respect to the eutopic tissue (P < 0.01). The reduced expression of Fas in the ectopic endometrium with the contemporary higher expression of Fas-Ligand in the corresponding cells suggests a possible immune privilege of this tissue. Similar content being viewed by others

Olive DL, Pritts EA. Treatment of endometriosis. N Engl J Med. 2001;345(4):266–275. Sørensen SS, Andersen LF, Lose G. Endometriosis by implantation: a complication of endometrial ablation. Lancet. 1994;343(8907):1226. Gleicher N, El-Roy A, Confino E, Friberg J. Abnormal autoantibodies in endometriosis: is endometriosis an autoimmune disease? Obstet Gynecol. 1987;70(1):115–122. Hill JA. Immunology and endometriosis. Fertil Steril. 1992;58(2):262–264. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267(5203):1456–62. Taylor HS, Fei X. Emx2 regulates mammalian reproduction by altering endometrial cell proliferation. Mol Endocrinol. 2005;19(11):2839–2846. Yang H, Taylor HS, Lei C, Cheng C, Zhang W. Hormonal regulation of galectin 3 in trophoblasts and its effects on endometrium. Reprod Sci. 2011;18(11):1118–1127. Taniguchi F, Kaponis A, Izawa M, et al. Apoptosis and endometriosis. Front Biosci. 2011;3:648–662. Penna I, Du H, Ferriani R, Taylor HS. Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells. Mol Hum Reprod. 2008;14(10):613–618. Pacchiarotti A, Caserta D, Sbracia M, Moscarini M. Expression of oct-4 and c-kit antigens in endometriosis. Fertil Steril. 2011;95(3):1171–1173. Song J, Rutherford T, Naftolin F, Brown S, Mor G. Hormonal regulation of apoptosis and the Fas and Fas ligand system in human endometrial cells. Mol Hum Reprod. 2002;8(5):447–455. Selam B, Kayisli UA, Mulayim N, Arici A. Regulation of Fas ligand expression by estradiol and progesterone in human endometrium. Biol Reprod. 2001;65(4):979–985. Otsuki Y. Apoptosis in human endometrium: apoptotic detection methods and signaling. Med Electron Microsc. 2001;34(3):166–173. Watanabe H, Kanzaki H, Narukawa S, et al. Bcl-2 and FAS expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis. Am J Obstet Gynecol. 1997;176(2):360–368. Yamashita H, Otsuki Y, Matsumoto K, Ueki K, Ueki M. Fas ligand, Fas antigen and Bcl-2expression in human endometrium during the menstrual cycle. Mol Hum Reprod. 1999;5(4):358–364. Harada M, Suganuma N, Furuhashi M, et al. Detection of apoptosis in human endometriotic tissues. Mol Hum Reprod. 1996;2(5):307–15. Garcia-Velasco JA, Mulayim N, Kayisli UA, Arici A. Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis. Fertil Steril. 2002;78(4):855–859. The American Fertility Society. Revised American Fertility Society classification of endometriosis:1985. Fertil Steril. 1985;43(3):351–352. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29(4):577–580. McCarty KS, Miller LS, Cox EB. Estrogen receptor analysis, correlation of biochemical and immunohistochemical methods using monoclonal anti-receptor antibodies. Arch Pathol Lab Med. 1985;109(8):716–721. Hopwood D, Levison DA. Atrophy and apoptosis in the cyclical human endometrium. J Pathol. 1976;119(3):159–166. Kokawa K, Shikone T, Nakano R. Apoptosis in the human uterine endometrium during the menstrual cycle. J Clin Endocrinol Metab. 1996;81(11):4144–4147. Illanes SE, Maisey K, Sandoval M. Fas ligand(+) fallopian tube epithelium induces apoptosis in both Fas receptor(+) T lymphocytes and endometrial cells. Fertil Steril. 2013:100(2):550–560. Tabibzadeh S, Zupi E, Babaknia A, Liu R, Marconi D, Romanini C. Site and menstrual cycle-dependent expression of proteins of the tumour necrosis factor (TNF) receptor family, and BCL-2oncoprotein and phase-specific production of TNF alpha in human endometrium. Hum Reprod. 1995;10(2):277–286. Sturlese E, Salmeri FM, Retto G, et al. Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. J Reprod Immunol. 2011;92(1–2):74–81. Chung HW, Wen Y, Chun SH, Nezhat C, Woo BH, Lake Polan M. Matrix metalloproteinase-9 andtissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium inwomen with endometriosis: a rationale for endometriotic invasiveness. Fertil Steril. 2001;75(1):152–159. Chung HW, Lee JY, Moon HS, et al. Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression inectopic and eutopic endometrium. Fertil Steril. 2002;78(4):787–795. Osteen KG, Yeaman GR, Bruner-Tran KL. Matrix metalloproteinases and endometriosis. Semin Reprod Med. 2003;21(2):155–164. Ueda M, Yamashita Y, Takehara M, et al. Survivin gene expression in endometriosis. J Clin Endocrinol Metab. 2002;87(7):3452–3459. Abreu-Martin MT, Vidrich A, Lynch DH, Targan SR. Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen. J Immunol. 1995;155(9):4147–4154. Arici A, Tazuke SI, Attar E, Kliman HJ, Olive DL. Interleukin-8 concentration in peritoneal fluidof patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells. Mol Hum Reprod. 1996;2(1):40–45. Kalu E, Sumar N, Giannopoulos T, et al. Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis. J Obstet Gynaecol Res. 2007;33(4):490–495. Selam B, Kayisli UA, Garcia-Velasco JA, Akbas GE, Arici A. Regulation of fas ligand expression by IL-8 in human endometrium. J Clin Endocrinol Metab. 2002;87(8):3921–3927. Gebel HM, Braun DP, Tambur A, Frame D, Rana N, Dmowski WP. Spontaneous apoptosis ofendometrial tissue is impaired in women with endometriosis. Fertil Steril. 1998;69(6):1042–1047. Gompel A, Sabourin JC, Martin A, et al. Bcl-2 expression in normal endometrium during the menstrual cycle. Am J Pathol. 1994;144(6):1195–1202. McLaren J, Prentice A, Charnock-Jones DS, Sharkey AM, Smith SK. Immunolocalization of the apoptosis regulating proteins bcl-2 and bax in human endometrium and isolated peritoneal fluid macrophages in endometriosis. Hum Reprod. 1997;12(1):146–152. Igarashi TM, Bruner-Tran KL, Yeaman GR, et al. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fertil Steril. 2005;84(1):67–74. Kayisli UA, Guzeloglu-Kayisli O, Arici A. Endocrine-immune interactions in human endometrium. Ann N Y Acad Sci. 2004;1034:50–63. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Sbracia, M., Valeri, C., Antonini, G. et al. Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis: The Possible Immune Privilege of Ectopic Endometrium. Reprod. Sci. 23, 81–86 (2016). https://doi.org/10.1177/1933719115594019 Published: Issue date: DOI: https://doi.org/10.1177/1933719115594019