Neue Aspekte zur Ätiologie und Pathogenese der Endometriose

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. Similar content being viewed by others Abbreviations - COX-2: - Cyclooxygenase 2 - PGE2 : - Prostaglandin E2 - P450arom: - Aromatase - StAR: - „steroidogenic acute regulatory protein“ - ERα: - Östrogenrezeptor α - ERβ: - Östrogenrezeptor β Literatur Guo SW, Wang Y (2006) The prevalence of endometriosis in women with chronic pelvic pain. Gynecol Obstet Invest 62:121–130 Guo SW (2009) Recurrence of endometriosis and its control. Hum Reprod Update 15:441–461 Sasson IE, Taylor HS (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci 1127:106–115 Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519 Bulun SE (2009) Endometriosis. N Engl J Med 360:268–279 Missmer SA, Hankinson SE, Spiegelman D et al (2004) In utero exposures and the incidence of endometriosis. Fertil Steril 82:1501–1508 Caserta D, Maranghi L, Mantovani A et al (2008) Impact of endocrine disruptor chemicals in gynaecology. Hum Reprod Update 14:59–72 Halme J, Hammond MG, Hulka JF et al (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 64:151–154 Leyendecker G, Kunz G, Noe M et al (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4:752–762 Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280:529–538 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 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 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 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 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 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 Kao LC, Tulac S, Lobo S et al (2002) Global gene profiling in human endometrium during the window of implantation. Endocrinology 143:2119–2138 Bulun SE, Gurates B, Fang Z et al (2002) Mechanisms of excessive estrogen formation in endometriosis. J Reprod Immunol 55:21–33 Pavone ME, Bulun SE (2012) Aromatase inhibitors for the treatment of endometriosis. Fertil Steril 98:1370–1379 Bulun SE, Monsavais D, Pavone ME et al (2012) Role of estrogen receptor-beta in endometriosis. Semin Reprod Med 30:39–45 Boney-Montoya J, Ziegler YS, Curtis CD et al (2010) Long-range transcriptional control of progesterone receptor gene expression. Mol Endocrinol 24:346–358 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 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 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 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 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 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 Giudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799 Lebovic DI, Mueller MD, Taylor RN (2001) Immunobiology of endometriosis. Fertil Steril 75:1–10 Gargett CE (2007) Review article: stem cells in human reproduction. Reprod Sci 14:405–424 Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311:1880–1885 Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13:87–101 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 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 Gotte M, Wolf M, Staebler A et al (2011) Aberrant expression of the pluripotency marker SOX-2 in endometriosis. Fertil Steril 95:338–341 Matthai C, Horvat R, Noe M et al (2006) Oct-4 expression in human endometrium. Mol Hum Reprod 12:7–10 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 Taylor HS (2004) Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 292:81–85 Du H, Taylor HS (2007) Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells 25:2082–2086 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 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. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article 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 Published: Issue date: DOI: https://doi.org/10.1007/s00129-014-3422-0 Schlüsselwörter - Eutopes Endometrium - Endometriale Stammzellen - Retrograde Menstruation - Progesteronresistenz - Hyperestrogenämie