Skip to main content
SpringerLink
Log in

Altered Biological Characteristics of Eutopic and Ectopic Endometrium

  • Chapter
  • First Online:
Endometriosis

  • 2327 Accesses

Abstract

As it has been presented thus far, the pathogenesis of endometriosis is complex and multifactorial. The intrinsic endometrial abnormalities thought to be associated with endometriosis include abnormal gene expression, altered endometrial responses to hormones such as progesterone, impaired immunological response, increased nerve density, and oxidative stress. Also interesting is the fact that such biological alterations have also been observed in the eutopic endometrium of patients with endometriosis, which strongly indicates their critical role in the pathophysiology of the disease. Indeed, it has been suggested that the evaluation of eutopic endometrium is an important line of investigation which may help to achieve a fuller understanding of endometriosis pathogenesis. Hence, we present herein a literature review and a comprehensive evaluation of the involvement of the eutopic endometrium in endometriosis. The biological characteristics of both eutopic and ectopic endometrial tissues as well as their clinical correlations with the disease are highlighted, with the primary objective of understanding the role of the eutopic endometrium in this enigmatic gynecological disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferenczy A, Bertrand G, Gelfand MM. Proliferation kinetics of human endometrium during the normal menstrual cycle. Am J Obstet Gynecol. 1979;133(8):859–67.

    CAS  PubMed  Google Scholar 

  2. Padykula HA. Regeneration in the primate uterus: the role of stem cells. Ann N Y Acad Sci. 1991;622:47–56.

    CAS  PubMed  Google Scholar 

  3. Brenner RM, Slayden OD, Rodgers WH, et al. Immunocytochemical assessment of mitotic activity with an antibody to phosphorylated histone H3 in the macaque and human endometrium. Hum Reprod. 2003;18(6):1185–93.

    CAS  PubMed  Google Scholar 

  4. Slayden OD, Brenner RM. Hormonal regulation and localization of estrogen, progestin and androgen receptors in the endometrium of nonhuman primates: effects of progesterone receptor antagonists. Arch Histol Cytol. 2004;67:393–409.

    CAS  PubMed  Google Scholar 

  5. Ponnampalam AP, Weston GC, Trajstman AC, et al. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol Hum Reprod. 2004;10(12):879–93.

    CAS  PubMed  Google Scholar 

  6. Thiruchelvam U, Dransfield I, Saunders PT, et al. The importance of the macrophage within the human endometrium. J Leukoc Biol. 2013;93(2):217–25.

    CAS  PubMed  Google Scholar 

  7. Giudice LC, Irwin JC. Roles of the insulin-like growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface. Semin Reprod Endocrinol. 1999;17(1):13–21.

    CAS  PubMed  Google Scholar 

  8. Healy DL, Hodgen GD. The endocrinology of human endometrium. Obstet Gynecol Surv. 1983;38(8):509–30.

    CAS  PubMed  Google Scholar 

  9. Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev. 1999;20(3):358–417.

    CAS  PubMed  Google Scholar 

  10. Wada-Hiraike O, Imamov O, Hiraike H, et al. Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A. 2006;103(8):2959–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Conneely OM, Mulac-Jericevic B, Lydon JP, et al. Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice. Mol Cell Endocrinol. 2001;179:97–103.

    CAS  PubMed  Google Scholar 

  12. Giudice LC. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine. Fertil Steril. 1994;61(1):1–17.

    CAS  PubMed  Google Scholar 

  13. Smith CL. Cross-talk between peptide growth factor and estrogen receptor signaling pathways. Biol Reprod. 1998;58:627–32.

    CAS  PubMed  Google Scholar 

  14. Gargett CE, Chan RW, Schwab KE. Hormone and growth factor signaling in endometrial renewal: role of stem/progenitor cells. Mol Cell Endocrinol. 2008;288(1–2):22–9.

    CAS  PubMed  Google Scholar 

  15. Arnold JT, Kaufman DG, Seppälä M, et al. Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum Reprod. 2001;16(5):836–45.

    CAS  PubMed  Google Scholar 

  16. Hull ML, Escareno CR, Godsland JM, et al. Endometrial-peritoneal interactions during endometriotic lesion establishment. Am J Pathol. 2008;173(3):700–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Donjacour AA, Cunha GR. Stromal regulation of epithelial function. Cancer Treat Res. 1991;53:335–64.

    CAS  PubMed  Google Scholar 

  18. Cooke PS, Buchanan DL, Young P, et al. Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci U S A. 1997;94(12):6535–40.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Witz CA. Pathogenesis of endometriosis. Gynecol Obstet Invest. 2002;53:52–62.

    PubMed  Google Scholar 

  20. Griffith JS, Rodgers AK, Schenken RS. Reviews: in vitro models to study the pathogenesis of endometriosis. Reprod Sci. 2010;17(1):5–12.

    CAS  PubMed  Google Scholar 

  21. Zhang H, Li M, Zheng X, et al. Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro. Mol Hum Reprod. 2009;15(10):653–63.

    CAS  PubMed  Google Scholar 

  22. Silveira CG, Abrão MS, Dias Jr JA, et al. Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells. Hum Reprod. 2012;27(11):3187–97.

    CAS  PubMed  Google Scholar 

  23. Guo SW. Epigenetics of endometriosis. Mol Hum Reprod. 2009;15(10):587–607.

    CAS  PubMed  Google Scholar 

  24. Clement PB, Young RH, Scully RE. Stromal endometriosis of the uterine cervix. A variant of endometriosis that may simulate a sarcoma. Am J Surg Pathol. 1990;14(5):449–55.

    CAS  PubMed  Google Scholar 

  25. Bulun SE, Cheng YH, Pavone ME, et al. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med. 2010;28(1):36–43.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Donnez J, Nisolle M, Smoes P, et al. Peritoneal endometriosis and “endometriotic” nodules of the rectovaginal septum are two different entities. Fertil Steril. 1996;66(3):362–8.

    CAS  PubMed  Google Scholar 

  27. Nisolle M, Donnez J. Progesterone receptors (PR) in ectopic endometrium? Fertil Steril. 1997;68(5):943–4.

    CAS  PubMed  Google Scholar 

  28. Matsuzaki S, Maleysson E, Darcha C. Analysis of matrix metalloproteinase-7 expression in eutopic and ectopic endometrium samples from patients with different forms of endometriosis. Hum Reprod. 2010;25(3):742–50.

    CAS  PubMed  Google Scholar 

  29. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9.

    CAS  PubMed  Google Scholar 

  30. Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 1927;3(2):93–110.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Ulukus M, Cakmak H, Arici A. The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006;13(7):467–76.

    CAS  PubMed  Google Scholar 

  32. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–58.

    CAS  PubMed  Google Scholar 

  33. Cramer DW, Missmer SA. The epidemiology of endometriosis. Ann N Y Acad Sci. 2002;955:11–22.

    PubMed  Google Scholar 

  34. Guo SW. Recurrence of endometriosis and its control. Hum Reprod Update. 2009;15(4):441–61.

    PubMed  Google Scholar 

  35. Bromer JG, Aldad TS, Taylor HS. Defining the proliferative phase endometrial defect. Fertil Steril. 2009;91(3):698–704.

    PubMed Central  PubMed  Google Scholar 

  36. Jones CJ, Inuwa IM, Nardo LG, et al. Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls - a pilot observational study. Reprod Sci. 2009;16(6):559–72.

    PubMed  Google Scholar 

  37. Arimoto T, Katagiri T, Oda K, et al. Genome-wide cDNA microarray analysis of gene-expression profiles involved in ovarian endometriosis. Int J Oncol. 2003;22(3):551–60.

    CAS  PubMed  Google Scholar 

  38. Kao LC, Germeyer A, Tulac S, et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003;144(7):2870–81.

    CAS  PubMed  Google Scholar 

  39. Matsuzaki S, Canis M, Vaurs-Barrière C, et al. DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection. Fertil Steril. 2005;84:1180–90.

    CAS  PubMed  Google Scholar 

  40. Matsuzaki S, Canis M, Pouly JL, et al. Analysis of aromatase and 17beta-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid expression in deep endometriosis and eutopic endometrium using laser capture microdissection. Fertil Steril. 2006;85(2):308–13.

    CAS  PubMed  Google Scholar 

  41. Burney RO, Talbi S, Hamilton AE, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–26.

    CAS  PubMed  Google Scholar 

  42. Sherwin JR, Sharkey AM, Mihalyi A, et al. Global gene analysis of late secretory phase, eutopic endometrium does not provide the basis for a minimally invasive test of endometriosis. Hum Reprod. 2008;23(5):1063–8.

    CAS  PubMed  Google Scholar 

  43. Laudanski P, Szamatowicz J, Kowalczuk O, et al. Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis. Hum Reprod. 2009;24(8):1880–90.

    CAS  PubMed  Google Scholar 

  44. Roobrouck VD, Ulloa-Montoya F, Verfaillie CM. Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res. 2008;314(9):1937–44.

    CAS  PubMed  Google Scholar 

  45. Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. 2008;1127:106–15.

    PubMed Central  PubMed  Google Scholar 

  46. Maruyama T, Masuda H, Ono M, et al. Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology. Reproduction. 2010;140(1):11–22.

    CAS  PubMed  Google Scholar 

  47. Figueira PG, Abrão MS, Krikun G, et al. Stem cells in endometrium and their role in the pathogenesis of endometriosis. Ann N Y Acad Sci. 2011;1221:10–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Vinatier D, Cosson M, Dufour P. Is endometriosis an endometrial disease? Eur J Obstet Gynecol Reprod Biol. 2000;91(2):113–25.

    CAS  PubMed  Google Scholar 

  49. Sharpe-Timms KL. Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci. 2001;943:131–47.

    CAS  PubMed  Google Scholar 

  50. Wu Y, Strawn E, Basir Z, et al. Genomic alterations in ectopic and eutopic endometria of women with endometriosis. Gynecol Obstet Invest. 2006;62(3):148–59.

    PubMed  Google Scholar 

  51. Hey-Cunningham AJ, Peters KM, Zevallos HB, et al. Angiogenesis, lymphangiogenesis and neurogenesis in endometriosis. Front Biosci (Elite Ed). 2013;5:1033–56.

    Google Scholar 

  52. Kyama CM, Mihalyi A, Simsa P, et al. Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis. Front Biosci (Elite Ed). 2009;1:444–54.

    Google Scholar 

  53. Hapangama DK, Turner MA, Drury J, et al. Aberrant expression of regulators of cell-fate found in eutopic endometrium is found in matched ectopic endometrium among women and in a baboon model of endometriosis. Hum Reprod. 2010;25(11):2840–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Afshar Y, Hastings J, Roqueiro D, et al. Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis. Biol Reprod. 2013;88(2):44.

    PubMed Central  PubMed  Google Scholar 

  55. Lee B, Du H, Taylor HS. Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009;80(1):79–85.

    PubMed Central  PubMed  Google Scholar 

  56. Pellegrini C, Gori I, Achtari C, et al. The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogen-regulated genes implicated in proliferation, is increased in peritoneal endometriosis. Fertil Steril. 2012;98(5):1200–8.

    CAS  PubMed  Google Scholar 

  57. Gashaw I, Hastings JM, Jackson KS, et al. Induced endometriosis in the baboon (Papio anubis) increases the expression of the proangiogenic factor CYR61 (CCN1) in eutopic and ectopic endometria. Biol Reprod. 2006;74(6):1060–6.

    CAS  PubMed  Google Scholar 

  58. Hastings JM, Jackson KS, Mavrogianis PA, et al. The estrogen early response gene FOS is altered in a baboon model of endometriosis. Biol Reprod. 2006;75(2):176–82.

    CAS  PubMed  Google Scholar 

  59. Hastings JM, Fazleabas AT. A baboon model for endometriosis: implications for fertility. Reprod Biol Endocrinol. 2006;4:S7.

    PubMed Central  PubMed  Google Scholar 

  60. Jackson KS, Brudney A, Hastings JM, et al. The altered distribution of the steroid hormone receptors and the chaperone immunophilin FKBP52 in a baboon model of endometriosis is associated with progesterone resistance during the window of uterine receptivity. Reprod Sci. 2007;14(2):137–50.

    CAS  PubMed  Google Scholar 

  61. Santamaria X, Massasa EE, Taylor HS. Migration of cells from experimental endometriosis to the uterine endometrium. Endocrinology. 2012;153(11):5566–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Garai J, Molnar V, Varga T, et al. Endometriosis: harmful survival of an ectopic tissue. Front Biosci. 2006;11:595–619.

    CAS  PubMed  Google Scholar 

  63. Huhtinen K, Desai R, Ståhle M, et al. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J Clin Endocrinol Metab. 2012;97(11):4228–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Hu WP, Tay SK, Zhao Y. Endometriosis-specific genes identified by real-time reverse transcription-polymerase chain reaction expression profiling of endometriosis versus autologous uterine endometrium. J Clin Endocrinol Metab. 2006;91(1):228–38.

    CAS  PubMed  Google Scholar 

  65. Wu Y, Kajdacsy-Balla A, Strawn E, et al. Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology. 2006;47(1):232–46.

    Google Scholar 

  66. Eyster KM, Klinkova O, Kennedy V, et al. Whole genome deoxyribonucleic acid microarray analysis of gene expression in ectopic versus eutopic endometrium. Fertil Steril. 2007;88(6):1505–33.

    CAS  PubMed  Google Scholar 

  67. Honda H, Barrueto FF, Gogusev J, et al. Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis. Reprod Biol Endocrinol. 2008;6:59.

    PubMed Central  PubMed  Google Scholar 

  68. Meola J, Rosa e Silva JC, Dentillo DB, et al. Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis. Fertil Steril. 2010;93(6):1750–73.

    CAS  PubMed  Google Scholar 

  69. Schweppe KW, Wynn RM, Beller FK. Ultrastructural comparison of endometriotic implants and eutopic endometrium. Am J Obstet Gynecol. 1984;148(7):1024–39.

    CAS  PubMed  Google Scholar 

  70. Yu CQ, Shi SF, Liu YH, et al. Primary culture and morphologic observation of eutopic and ectopic endometrial cells from patients with endometriosis. Zhong Xi Yi Jie He Xue Bao. 2006;4(2):189–93.

    PubMed  Google Scholar 

  71. Chen HW, Tzeng CR. Applications of microarray in reproductive medicine. Chang Gung Med J. 2006;29(1):15–24.

    PubMed  Google Scholar 

  72. Matsuzaki S. DNA microarray analysis in endometriosis for development of more effective targeted therapies. Front Biosci (Elite Ed). 2011;3:1139–53.

    Google Scholar 

  73. Bulun SE, Adashi EY. The physiology and pathology of the female reproductive axis. In: Larsen PR, Kronenberg HM, Melmed S, et al., editors. Williams textbook of endocrinology. 10th ed. Philadelphia: WB Saunders; 2003. p. 587–664.

    Google Scholar 

  74. Rogers PAW, D’Hooghe TM, Fazleabas A, et al. Priorities for endometriosis research: recommendations from an International consensus workshop. Reprod Sci. 2009;16:335–46.

    PubMed Central  PubMed  Google Scholar 

  75. Khan MA, Sengupta J, Mittal S, et al. Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis. Reprod Biol Endocrinol. 2012;10:84.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Pan Q, Luo X, Toloubeydokhti T, et al. The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression. Mol Hum Reprod. 2007;13(11):797–806.

    CAS  PubMed  Google Scholar 

  77. Teague EM, Print CG, Hull ML. The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update. 2010;16(2):142–65.

    PubMed  Google Scholar 

  78. Filigheddu N, Gregnanin I, Porporato PE, et al. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol. 2010;2010(369549).

    Google Scholar 

  79. Bharadwaj Siva A, Srivastava P, Shivaji S. Understanding the pathogenesis of endometriosis through proteomics: recent advances and future prospects. Proteomics Clin Appl. 2014;8(1–2):86–98

    Google Scholar 

  80. Chehna-Patel N, Sachdeva G, Gajbhiye R, et al. “Spot”-ting differences between the ectopic and eutopic endometrium of endometriosis patients. Fertil Steril. 2010;94(6):1964–71.

    PubMed  Google Scholar 

  81. Klemmt PA, Carver JG, Koninckx P, et al. Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression. Hum Reprod. 2007;22(12):3139–47.

    PubMed  Google Scholar 

  82. Halme J, Hammond MG, Hulka JF, Raj S, Talbert LM. Increased activation of pelvic macrophages in infertile women with endometriosis. Obstet Gynecol. 1984;64:151–4.

    CAS  PubMed  Google Scholar 

  83. Keettel WC, Stein RJ. The viability of the cast-off menstrual endometrium. Am J Obstet Gynecol. 1951;61:440.

    CAS  PubMed  Google Scholar 

  84. Nisolle M, Berliere M, Paindaveine B, Casanas-Roux F, Bourdon A, Donnez J. Histologic study of peritoneal endometriosis in infertile women. Fertil Steril. 1990;53:984–8.

    CAS  PubMed  Google Scholar 

  85. Kruitwagen RFPM, Poels LG, Willemsen WNP, de Ronde IJ, Jap PH, Rolland R. Endometrial epithelial cells in peritoneal fluid during the early follicular phase. Fertil Steril. 1991;55:297–303.

    CAS  PubMed  Google Scholar 

  86. Arumugam K, Lim JM. Menstrual characteristics associated with endometriosis. Br J Obstet Gynecol. 1997;104:948–50.

    CAS  Google Scholar 

  87. Vercellini P, De Giorgo O, Aimi G, Panazza S, Uglietti A, Crosignani PG. Menstrual characteristics in women with and without endometriosis. Obstet Gynecol. 1997;90:264–8.

    CAS  PubMed  Google Scholar 

  88. Vinatier D, Orazi G, Cosson M, Dufour P. Theories of endometriosis. Eur J Obstet Gynecol Reprod Biol. 2001;96:21–34.

    CAS  PubMed  Google Scholar 

  89. 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;74:760–6.

    CAS  PubMed  Google Scholar 

  90. Aplin AE, Howe A, Alahari SK, Juliano RL. Signal transduction and signal modulation by cell adhesion receptors: the role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacol Rev. 1998;50:197–263.

    CAS  PubMed  Google Scholar 

  91. González-Ramos DJ, Defrère S, et al. Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis. Mol Hum Reprod. 2007;13:503–9.

    PubMed  Google Scholar 

  92. González-Ramos R, Van Langendonckt A, Defrère S, et al. Agents blocking the nuclear factor-kappaB pathway are effective inhibitors of endometriosis in an in vivo experimental model. Gynecol Obstet Invest. 2008;65(3):174–86.

    PubMed  Google Scholar 

  93. Murk W, Atabekoglu CS, Cakmak H, et al. Extracellularly signal-regulated kinase activity in the human endometrium: possible roles in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2008;93(9):3532–40.

    CAS  PubMed  Google Scholar 

  94. Kosugi Y, Elias S, Malinak LR, et al. Increased heterogeneity of chromosome 17 aneuploidy in endometriosis. Am J Obstet Gynecol. 1999;180:792–7.

    CAS  PubMed  Google Scholar 

  95. Jiang X, Morland SJ, Hitchcock A, Thomas EJ, Campbell IG. Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage. Cancer Res. 1998;58:1707–12.

    CAS  PubMed  Google Scholar 

  96. Obata K, Morland SJ, Watson RH, et al. Frequent PTEN/MMAC mutations in endometrioid, but not serous or mucinous epithelial ovarian tumors. Cancer Res. 1998;58:2095–7.

    CAS  PubMed  Google Scholar 

  97. Braun DP, Ding J, Shaheen F, Willey JC, Rana N, Dmowski WP. Quantitative expression of apoptosis-regulating genes in endometrium from women with and without endometriosis. Fertil Steril. 2007;87(2):263–8.

    CAS  PubMed  Google Scholar 

  98. Othman EE, Salama S, Ismail N, Al-Hendy A. Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells. Fertil Steril. 2007;88(2):462–71.

    CAS  PubMed  Google Scholar 

  99. Witz CA, Allsup KT, Montoya-Rodriguez IA, Vaughan SL, Centonze VE, Schenken RS. Pathogenesis of endometriosis–current research. Hum Fertil (Camb). 2003;6:34–40.

    Google Scholar 

  100. Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features. Am J Surg Pathol. 1992;16:600–10.

    CAS  PubMed  Google Scholar 

  101. Blumenfeld Z. Hormonal suppressive therapy for endometriosis may not improve patient health. Fertil Steril. 2004;81:487–92.

    CAS  PubMed  Google Scholar 

  102. Ridley JH. Primary adenocarcinoma in implant of endometriosis. Obstet Gynecol. 1966;27:261–7.

    CAS  PubMed  Google Scholar 

  103. Czernobilsky B, Silverman BB, Mikuta JJ. Endometrioid carcinoma of the ovary. A clinicopathologic study of 75 cases. Cancer. 1970;26:1141–52.

    CAS  PubMed  Google Scholar 

  104. Czernobilsky B, Silverman BB, Enterline HT. Clear-cell carcinoma of the ovary. A clinicopathologic analysis of pure and mixed forms and comparison with endometrioid carcinoma. Cancer. 1970;25:762–72.

    CAS  PubMed  Google Scholar 

  105. Czernobilsky B, Morris WJ. A histologic study of ovarian endometriosis with emphasis on hyperplastic and atypical changes. Obstet Gynecol. 1979;53:318–23.

    CAS  PubMed  Google Scholar 

  106. Matsumoto K, Wolffe AP. Gene regulation by Y-box proteins: coupling control of transcription and translation. Trends Cell Biol. 1998;8:318–23.

    CAS  PubMed  Google Scholar 

  107. Kohno K, Izumi H, Uchiumi T, Ashizuka M, Kuwano M. The pleiotropic functions of the Y-box binding protein, YB-1. Bioessays. 2003;25:691–8.

    CAS  PubMed  Google Scholar 

  108. Lage H, Surowiak P, Holm PS. YB-1 as a potential target in cancer therapy. Pathologe. 2008;29:187–90.

    PubMed  Google Scholar 

  109. Chatterjee M, Rancso C, Stuhmer T, et al. The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma. Blood. 2008;111:3714–22.

    CAS  PubMed  Google Scholar 

  110. Bargou RC, Jurchott K, Wagener C, et al. Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression. Nat Med. 1997;3:447–50.

    CAS  PubMed  Google Scholar 

  111. Wu J, Lee C, Yokom D, et al. Disruption of the Y-box binding protein-1 results in suppression of the epidermal growth factor receptor and HER-2. Cancer Res. 2006;66:4872–9.

    CAS  PubMed  Google Scholar 

  112. Fujii T, Yokoyama G, Takahashi H, et al. Preclinical and clinical studies of novel breast cancer drugs targeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-1. Curr Med Chem. 2008;15:528–37.

    CAS  PubMed  Google Scholar 

  113. Habibi G, Leung S, Law JH, et al. Redefining prognostic factors for breast cancer: YB-1 is a stronger predictor of relapse and disease-specific survival than estrogen receptor or HER-2 across all tumor subtypes. Breast Cancer Res. 2008;10:R86.

    PubMed Central  PubMed  Google Scholar 

  114. Silveira CG, Krampe J, Ruhland B, Diedrich K, Hornung D, Agic A. Cold Shock Domain Family Member YB-1 Expression in Endometrium and Endometriosis. Hum Reprod. 2012;27(1):173–82.

    CAS  PubMed  Google Scholar 

  115. Schachner M. Neural recognition molecules and synaptic plasticity. Curr Opin Cell Biol. 1997;9:627–34.

    CAS  PubMed  Google Scholar 

  116. Montgomery AM, Becker JC, Siu CH, et al. Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. J Cell Biol. 1996;132:475–85.

    CAS  PubMed  Google Scholar 

  117. Hortsch M. Structural and functional evolution of the L1 family: are four adhesion molecules better than one? Mol Cell Neurosci. 2000;15:1–10.

    CAS  PubMed  Google Scholar 

  118. Meier F, Busch S, Gast D, et al. The adhesion molecule L1 (CD171) promotes melanoma progression. Int J Cancer. 2006;119:549–55.

    CAS  PubMed  Google Scholar 

  119. Huszar M, Moldenhauer G, Gschwend V, et al. Expression profile analysis in multiple human tumors identifies L1 (CD171) as a molecular marker for differential diagnosis and targeted therapy. Hum Pathol. 2006;37:1000–8.

    CAS  PubMed  Google Scholar 

  120. Kaifi JT, Strelow A, Schurr PG, et al. L1 (CD171) is highly expressed in gastrointestinal stromal tumors. Mod Pathol. 2006;19:399–406.

    CAS  PubMed  Google Scholar 

  121. Fogel M, Gutwein P, Mechtersheimer S, et al. L1CAM expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003;362:869–75.

    CAS  PubMed  Google Scholar 

  122. Ohnishi T, Matsumura H, Izumoto S, et al. A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res. 1998;58:2935–40.

    CAS  PubMed  Google Scholar 

  123. Mechtersheimer S, Gutwein P, Agmon-Levin N, et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J Cell Biol. 2001;155:661–73.

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Felding-Habermann B, Silletti S, Mei F, et al. A single immunoglobulin-like domain of the human neural cell adhesion molecule L1 supports adhesion by multiple vascular and platelet integrins. J Cell Biol. 1997;139:1567–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Finas D, Huszar M, Agic A, et al. L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis. Hum Reprod. 2008;23(5):1053–62.

    CAS  PubMed  Google Scholar 

  126. Kao LC, Tulac S, Lobo S, et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002;143(6):2119–38.

    CAS  PubMed  Google Scholar 

  127. Vercellini P, Cortesi I, Crosignani PG. Progestins for symptomatic endometriosis: a critical analysis of the evidence. Fertil Steril. 1997;68(3):393–401.

    CAS  PubMed  Google Scholar 

  128. Hornung D, Ryan IP, Chao VA, Vigne JL, Schriock ED, Taylor RN. Immunolocalization and regulation of the chemokine RANTES in human endometrial and endometriosis tissues and cells. J Clin Endocrinol Metab. 1997;82(5):1621–8.

    CAS  PubMed  Google Scholar 

  129. Zeitoun KM, Bulun SE. Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril. 1999;72(6):961–9.

    CAS  PubMed  Google Scholar 

  130. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996;93(12):5925–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996;392(1):49–53.

    CAS  PubMed  Google Scholar 

  132. Green S, Walter P, Kumar V, et al. Human oestrogen receptor cDNA: sequence, expression and homology to verb-A. Nature. 1996;320(6058):134–9.

    Google Scholar 

  133. Hewitt SC, Harrell JC, Korach KS. Lessons in estrogen biology from knockout and transgenic animals. Annu Rev Physiol. 2005;67:285–308.

    CAS  PubMed  Google Scholar 

  134. Korach KS, Emmen JM, Walker VR, et al. Update on animal models developed for analyses of estrogen receptor biological activity. J Steroid Biochem Mol Biol. 2003;86(3–5):387–91.

    CAS  PubMed  Google Scholar 

  135. Brandenberger AW, Lebovic DI, Tee MK, et al. Oestrogen receptor (ER)-alpha and ER-beta isoforms in normal endometrial and endometriosis-derived stromal cells. Mol Hum Reprod. 1999;5(7):651–5.

    CAS  PubMed  Google Scholar 

  136. Fujimoto J, Hirose R, Sakaguchi H, Tamaya T. Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata. Mol Hum Reprod. 1999;8:742–7.

    Google Scholar 

  137. Bulun SE, Cheng YH, Yin P, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248(1–2):94–103.

    CAS  PubMed  Google Scholar 

  138. Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab. 2000;85(8):2897–902.

    CAS  PubMed  Google Scholar 

  139. Lin Z, Reierstad S, Huang CC, Bulun SE. Novel estrogen receptor-alpha binding sites and estradiol target genes identified by chromatin immunoprecipitation cloning in breast cancer. Cancer Res. 2007;67(10):5017–24.

    CAS  PubMed  Google Scholar 

  140. Schultz JR, Petz LN, Nardulli AM. Cell- and ligand-specific regulation of promoters containing activator protein-1 and Sp1 sites by estrogen receptors alpha and beta. J Biol Chem. 2005;280(1):347–54.

    CAS  PubMed  Google Scholar 

  141. Tranguch S, Wang H, Daikoku T, Xie H, Smith DF, Dey SK. FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific. J Clin Invest. 2007;117:1824–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Aghajanova L, Velarde MC, Giudice LC. The progesterone receptor coactivator Hic-5 is involved in the pathophysiology of endometriosis. Endocrinology. 2009;150:3863–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Kastner P, Krust A, Turcotte B, et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990;9(5):1603–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Nardulli AM, Greene GL, O’Malley BW, Katzenellenbogen BS. Regulation of progesterone receptor messenger ribonucleic acid and protein levels in MCF-7 cells by estradiol: analysis of estrogen’s effect on progesterone receptor synthesis and degradation. Endocrinology. 1988;122(3):935–44.

    CAS  PubMed  Google Scholar 

  145. Wei LL, Krett NL, Francis MD, et al. Multiple human progesterone receptor messenger ribonucleic acids and their autoregulation by progestin agonists and antagonists in breast cancer cells. Mol Endocrinol. 1988;2(1):62–72.

    CAS  PubMed  Google Scholar 

  146. Read LD, Snider CE, Miller JS, Greene GL, Katzenellenbogen BS. Ligand-modulated regulation of progesterone receptor messenger ribonucleic acid and protein in human breast cancer cell lines. Mol Endocrinol. 1988;2(3):263–71.

    CAS  PubMed  Google Scholar 

  147. Petz LN, Ziegler YS, Schultz JR, Nardulli AM. Fos and Jun inhibit estrogen-induced transcription of the human progesterone receptor gene through an activator protein-1 site. Mol Endocrinol. 2004;18(3):521–32.

    CAS  PubMed  Google Scholar 

  148. Matthews J, Wihlén B, Tujague M, Wan J, Ström A, Gustafsson JA. Estrogen receptor (ER) beta modulates ERalpha-mediated transcriptional activation by altering the recruitment of c-Fos and c-Jun to estrogen-responsive promoters. Mol Endocrinol. 2006;20(3):534–43.

    CAS  PubMed  Google Scholar 

  149. Petz LN, Ziegler YS, Schultz JR, Kim H, Kemper JK, Nardulli AM. Differential regulation of the human progesterone receptor gene through an estrogen response element half site and Sp1 sites. J Steroid Biochem Mol Biol. 2004;88(2):113–22.

    CAS  PubMed  Google Scholar 

  150. Petz LN, Nardulli AM. Sp1 binding sites and an estrogen response element half-site are involved in regulation of the human progesterone receptor A promoter. Mol Endocrinol. 2000;14(7):972–85.

    CAS  PubMed  Google Scholar 

  151. Petz LN, Ziegler YS, Loven MA, Nardulli AM. Estrogen receptor alpha and activating protein-1 mediate estrogen responsiveness of the progesterone receptor gene in MCF-7 breast cancer cells. Endocrinology. 2002;143(12):4583–91.

    CAS  PubMed  Google Scholar 

  152. Schultz JR, Petz LN, Nardulli AM. Estrogen receptor alpha and Sp1 regulate progesterone receptor gene expression. Mol Cell Endocrinol. 2003;201(1–2):165–75.

    CAS  PubMed  Google Scholar 

  153. Savouret JF, Bailly A, Misrahi M, et al. Characterization of the hormone responsive element involved in the regulation of the progesterone receptor gene. EMBO J. 1991;10(7):1875–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  154. Montano MM, Kraus WL, Katzenellenbogen BS. Identification of a novel transferable cis element in the promoter of an estrogen-responsive gene that modulates sensitivity to hormone and antihormone. Mol Endocrinol. 1997;11(3):330–41.

    CAS  PubMed  Google Scholar 

  155. Scott RE, Wu-Peng XS, Yen PM, Chin WW, Pfaff DW. Interactions of estrogen- and thyroid hormone receptors on a progesterone receptor estrogen response element (ERE) sequence: a comparison with the vitellogenin A2 consensus ERE. Mol Endocrinol. 1997;11(11):1581–92.

    CAS  PubMed  Google Scholar 

  156. Osuga Y, Koga K, Hirota Y, Hirata T, Yoshino O, Taketani Y. Lymphocytes in endometriosis. Am J Reprod Immunol. 2011;65:1–10.

    PubMed  Google Scholar 

  157. Berbic M, Fraser IS. Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. J Reprod Immunol. 2011;88:149–55.

    CAS  PubMed  Google Scholar 

  158. Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem. 2011;18:200–8.

    CAS  PubMed  Google Scholar 

  159. Gonzalez-Ramos R, Van Langendonckt A, Defrere S, et al. Involvement of the nuclear factorκB pathway in the pathogenesis of endometriosis. Fertil Steril. 2010;94:1985–94.

    CAS  PubMed  Google Scholar 

  160. Barbieri RL, Niloff JM, Bast Jr RC, Scaetzl E, Kistner RW, Knapp RC. Elevated serum concentrations of CA-125 in patients with advanced endometriosis. Fertil Steril. 1986;45:630–4.

    CAS  PubMed  Google Scholar 

  161. Abrao MS, Podgaec S, Filho BM, Ramos LO, Pinotti JA, de Oliveira RM. The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod. 1997;12:2523–7.

    CAS  PubMed  Google Scholar 

  162. Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update. 1998;4:741–51.

    CAS  PubMed  Google Scholar 

  163. Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol. 2011;73:163–82.

    CAS  PubMed  Google Scholar 

  164. Al-Jefout M, Dezarnaulds G, Cooper M, et al. Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study. Hum Reprod. 2009;24(12):3019–24.

    CAS  PubMed  Google Scholar 

  165. Bokor A, Kyama CM, Vercruysse L, et al. Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis. Hum Reprod. 2009;24(12):3025–32.

    CAS  PubMed  Google Scholar 

  166. Newman TA, Bailey JL, Stocker LJ, Woo YL, Macklon NS, Cheong YC. Expression of neuronal markers in the endometrium of women with and those without endometriosis. Hum Reprod. 2013;28(9):2502–10.

    CAS  PubMed  Google Scholar 

  167. Leslie C, Ma T, McElhinney B, Leake R, Stewart CJ. Is the detection of endometrial nerve fibers useful in the diagnosis of endometriosis? Int J Gynecol Pathol. 2013;32(2):149–55.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University of Lübeck, Lübeck, Germany

    Cássia G. T. Silveira & Daniela Hornung

  2. Department of Gynecology and Obstetrics, Diakonissenkrankenhaus Karlsruhe Rüppurr, Diakonissenstr. 28, 76199, Karlsruhe, Germany

    Admir Agic & Daniela Hornung

  3. Geneva Foundation for Medical Education and Research, Versoix, Switzerland

    Geraldine O. Canny

Authors
  1. Cássia G. T. Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Admir Agic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geraldine O. Canny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Hornung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniela Hornung .

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Tottori, Japan

    Tasuku Harada

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Silveira, C.G.T., Agic, A., Canny, G.O., Hornung, D. (2014). Altered Biological Characteristics of Eutopic and Ectopic Endometrium. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_17

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54421-0_17

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54420-3

  • Online ISBN: 978-4-431-54421-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation