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Neue Aspekte zur Ätiologie und Pathogenese der Endometriose

New aspects of the etiology and pathogenesis of endometriosis

  • Leitthema
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Hintergrund

Endometriose stellt durch die vielfältige Morphologie und diverse Beschwerdebilder eine schwierig fassbare Entität dar. Ihre Entstehung ist noch teilweise ungeklärt.

Stand der Forschung

Fest steht, dass uterine Dysperistalsis eine verstärkte retrograde Menstruation nach sich zieht, was für Oberflächenschädigung am Peritoneum prädisponiert und so wohl die Implantation disseminierter endometrialer Zellen erleichtert wird. Das eutope Endometrium von Frauen mit Endometriose zeigt viele Veränderungen im Vergleich zu Kontrollen, die ektopen endometrialen Zellen der Endometrioseläsionen selbst haben ein verändertes Potenzial für Adhäsion, Invasion und Proliferation. Neben der Fähigkeit zur lokalen Östrogensynthese und relativen Progesteronresistenz weisen rezente Studien auf die Bedeutung epigenetischer Veränderungen hin. Durch die immunologische Dysfunktion bei Endometriose besteht einerseits eine verminderte lokale Immunreaktion mit reduzierter peritonealer Clearance, welche die Implantation von endometrialen Zellen nach retrograder Menstruation erleichtert, andererseits unterstützt ein proinflammatorisches Mikromilieu die Etablierung von Endometrioseläsionen; beide Mechanismen sind für die Ätiologie und Pathogenese zentral.

Ausblick

Rezente Studien deuten zunehmend auf eine Beteiligung von endometrialen Stammzellen hin. Aufgrund ihres hohen proliferativen Potenzials, erweiterter Differenzierungsmöglichkeiten und der enormen Regenerationsfähigkeit begünstigen endometriale Stammzellen die Entstehung von Endometriose.

Abstract

Background

Endometriosis is one of the most common benign diseases in the field of gynecology; however, after years of extensive research the pathogenesis remains enigmatic.

State of research

It is known that increased retrograde menstruation caused by uterine dysperistalsis and hyperpersistalsis and subsequent increased oxidative stress on the peritoneal mesothelium are vital factors facilitating the implantation of disseminated endometrial cells and endometriotic lesion formation. The eutopic endometrium in endometriosis patients appears to have a differential protein expression when compared to controls and ectopic endometrial cells of endometriotic lesions exhibit an altered potential for adhesion, invasion and proliferation. The capability for local estrogen biosynthesis and relative progesterone resistance as well as recently demonstrated epigenetic alterations of endometrial cells are key features for the development of this disease. Endometriosis is associated with an immunological dysfunction. Impaired immunosurveillance and peritoneal clearance on the one hand and the proinflammatory microenvironment on the other hand are considered to be key factors for the development of endometriotic lesions.

Perspectives

Recent data indicate the relevance of endometrial stem cells in the etiology and pathogenesis of endometriosis. Due to the high proliferative potential, extended cell differentiation capacity and tremendous ability for regeneration, endometrial stem cells are in the focus of research activities.

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Abb. 1

Abbreviations

COX-2:

Cyclooxygenase 2

PGE2 :

Prostaglandin E2

P450arom:

Aromatase

StAR:

„steroidogenic acute regulatory protein“

ERα:

Östrogenrezeptor α

ERβ:

Östrogenrezeptor β

Literatur

  1. Guo SW, Wang Y (2006) The prevalence of endometriosis in women with chronic pelvic pain. Gynecol Obstet Invest 62:121–130

    Article  PubMed  Google Scholar 

  2. Guo SW (2009) Recurrence of endometriosis and its control. Hum Reprod Update 15:441–461

    Article  PubMed  Google Scholar 

  3. Sasson IE, Taylor HS (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci 1127:106–115

    Article  PubMed Central  PubMed  Google Scholar 

  4. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519

    Article  CAS  PubMed  Google Scholar 

  5. Bulun SE (2009) Endometriosis. N Engl J Med 360:268–279

    Article  CAS  PubMed  Google Scholar 

  6. Missmer SA, Hankinson SE, Spiegelman D et al (2004) In utero exposures and the incidence of endometriosis. Fertil Steril 82:1501–1508

    Article  PubMed  Google Scholar 

  7. Caserta D, Maranghi L, Mantovani A et al (2008) Impact of endocrine disruptor chemicals in gynaecology. Hum Reprod Update 14:59–72

    Article  CAS  PubMed  Google Scholar 

  8. Halme J, Hammond MG, Hulka JF et al (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 64:151–154

    CAS  PubMed  Google Scholar 

  9. Leyendecker G, Kunz G, Noe M et al (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4:752–762

    Article  CAS  PubMed  Google Scholar 

  10. Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280:529–538

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Kunz G, Beil D, Deininger H et al (1996) The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod 11:627–632

    Article  CAS  PubMed  Google Scholar 

  12. Leyendecker G, Kunz G, Herbertz M et al (2004) Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci 1034:338–355

    Article  PubMed  Google Scholar 

  13. Kunz G, Beil D, Huppert P, Leyendecker G (2000) Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod 15:76–82

    Article  CAS  PubMed  Google Scholar 

  14. Wolfler MM, Meinhold-Heerlein IM, Henkel C et al (2013) Reduced hemopexin levels in peritoneal fluid of patients with endometriosis. Fertil Steril 100:777–781

    Article  PubMed  Google Scholar 

  15. Van Langendonckt A, Casanas-Roux F, Donnez J (2002) Iron overload in the peritoneal cavity of women with pelvic endometriosis. Fertil Steril 78:712–718

    Article  Google Scholar 

  16. Kastner P, Krust A, Turcotte B et al (1990) Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 9:1603–1614

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Kao LC, Tulac S, Lobo S et al (2002) Global gene profiling in human endometrium during the window of implantation. Endocrinology 143:2119–2138

    Article  CAS  PubMed  Google Scholar 

  18. Bulun SE, Gurates B, Fang Z et al (2002) Mechanisms of excessive estrogen formation in endometriosis. J Reprod Immunol 55:21–33

    Article  CAS  PubMed  Google Scholar 

  19. Pavone ME, Bulun SE (2012) Aromatase inhibitors for the treatment of endometriosis. Fertil Steril 98:1370–1379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Bulun SE, Monsavais D, Pavone ME et al (2012) Role of estrogen receptor-beta in endometriosis. Semin Reprod Med 30:39–45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Boney-Montoya J, Ziegler YS, Curtis CD et al (2010) Long-range transcriptional control of progesterone receptor gene expression. Mol Endocrinol 24:346–358

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  23. Eaton JL, Unno K, Caraveo M et al (2013) Increased AKT or MEK1/2 activity influences progesterone receptor levels and localization in endometriosis. J Clin Endocrinol Metab 98:E1871–E1879

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Hayashi A, Tanabe A, Kawabe S et al (2012) Dienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosis. J Ovarian Res 5:31

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Yamanaka K, Xu B, Suganuma I et al (2012) Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E(2) production in human endometriotic stromal cells in spheroid culture. Fertil Steril 97:477–482

    Article  CAS  PubMed  Google Scholar 

  26. Bruner-Tran KL, Herington JL, Duleba AJ et al (2013) Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology. Minerva Ginecol 65:199–213

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Osteen KG, Bruner-Tran KL, Eisenberg E (2005) Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis. Fertil Steril 83:529–537

    Article  CAS  PubMed  Google Scholar 

  28. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799

    Article  PubMed  Google Scholar 

  29. Lebovic DI, Mueller MD, Taylor RN (2001) Immunobiology of endometriosis. Fertil Steril 75:1–10

    Article  CAS  PubMed  Google Scholar 

  30. Gargett CE (2007) Review article: stem cells in human reproduction. Reprod Sci 14:405–424

    Article  CAS  PubMed  Google Scholar 

  31. Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311:1880–1885

    Article  CAS  PubMed  Google Scholar 

  32. Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13:87–101

    Article  CAS  PubMed  Google Scholar 

  33. Masuda H, Matsuzaki Y, Hiratsu E et al (2010) Stem cell-like properties of the endometrial side population: implication in endometrial regeneration. PLoS One 5:e10387

    Article  PubMed Central  PubMed  Google Scholar 

  34. Schwab KE, Chan RW, Gargett CE (2005) Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle. Fertil Steril 84(Suppl 2):1124–1130

    Article  CAS  PubMed  Google Scholar 

  35. Gotte M, Wolf M, Staebler A et al (2011) Aberrant expression of the pluripotency marker SOX-2 in endometriosis. Fertil Steril 95:338–341

    Article  PubMed  Google Scholar 

  36. Matthai C, Horvat R, Noe M et al (2006) Oct-4 expression in human endometrium. Mol Hum Reprod 12:7–10

    Article  CAS  PubMed  Google Scholar 

  37. Chang JH, Au HK, Lee WC et al (2013) Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis. Fertil Steril 99:1332–1339 e1335

    Article  CAS  PubMed  Google Scholar 

  38. Taylor HS (2004) Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 292:81–85

    Article  CAS  PubMed  Google Scholar 

  39. Du H, Taylor HS (2007) Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells 25:2082–2086

    Article  CAS  PubMed  Google Scholar 

  40. Forte A, Cipollaro M, Galderisi U (2014) Genetic, epigenetic and stem cell alterations in endometriosis: new insights and potential therapeutic perspectives. Clin Sci (Lond) 126:123–138

    Article  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M.M. Wölfler, P. Klein, M. Zalewski und N. Maass geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Universitätsklinik für Frauenheilkunde und Geburtshilfe, Medizinische Universität Graz, Auenbruggerplatz 14, 8036, Graz, Österreich

    M.M. Wölfler

  2. Frauenklinik für Gynäkologie und Geburtsmedizin, Universitätsklinikum der RWTH Aachen, Aachen, Deutschland

    M.M. Wölfler, M. Zalewski & N. Maass

  3. Klinik für Frauenheilkunde und Geburtshilfe, Kreiskrankenhaus Dormagen, Dormagen, Deutschland

    P. Klein

Authors
  1. M.M. Wölfler
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  2. P. Klein
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  3. M. Zalewski
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  4. N. Maass
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Correspondence to M.M. Wölfler.

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Wölfler, M., Klein, P., Zalewski, M. et al. Neue Aspekte zur Ätiologie und Pathogenese der Endometriose. Gynäkologe 48, 209–215 (2015). https://doi.org/10.1007/s00129-014-3422-0

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  • DOI: https://doi.org/10.1007/s00129-014-3422-0

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