Skip to main content
Log in

Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Introduction

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity.

Materials and Methods

The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder.

Conclusions

In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Koninckx PR (1999) The physiopathology of endometriosis: pollution and dioxin. Gynecol Obstet Invest 47(Suppl 1):47–49 (discussion 50)

    Article  PubMed  CAS  Google Scholar 

  2. Donnez J et al (2002) The efficacy of medical and surgical treatment of endometriosis-associated infertility and pelvic pain. Gynecol Obstet Invest 54(Suppl 1):2–7 (discussion 7–10)

    Article  PubMed  Google Scholar 

  3. Defrere S et al (2008) Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod 14(7):377–385

    Article  PubMed  CAS  Google Scholar 

  4. Sampson JA (1927) Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 3(2):93.43–110.43

    Google Scholar 

  5. Vinatier D et al (2001) Theories of endometriosis. Eur J Obstet Gynecol Reprod Biol 96(1):21–34

    Article  PubMed  CAS  Google Scholar 

  6. Fujii S (1991) Secondary mullerian system and endometriosis. Am J Obstet Gynecol 165(1):219–225

    PubMed  CAS  Google Scholar 

  7. Reese KA, Reddy S, Rock JA (1996) Endometriosis in an adolescent population: the Emory experience. J Pediatr Adolesc Gynecol 9(3):125–128

    PubMed  CAS  Google Scholar 

  8. Agarwal A, Gupta S, Sharma RK (2005) Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 3:28

    Article  PubMed  Google Scholar 

  9. Kennedy S, Mardon H, Barlow D (1995) Familial endometriosis. J Assist Reprod Genet 12(1):32–34

    Article  PubMed  CAS  Google Scholar 

  10. Yang WC et al (2004) Serum and endometrial markers. Best Pract Res Clin Obstet Gynaecol 18(2):305–318

    Article  PubMed  Google Scholar 

  11. Augoulea A et al (2009) The role of the oxidative-stress in the endometriosis-related infertility. Gynecol Endocrinol 25(2):75–81

    Article  PubMed  Google Scholar 

  12. Christodoulakos G et al (2007) Pathogenesis of endometriosis: the role of defective ‘immunosurveillance’. Eur J Contracept Reprod Health Care 12(3):194–202

    Article  PubMed  CAS  Google Scholar 

  13. Frey GH (1957) The familial occurrence of endometriosis; report of five instances and review of the literature. Am J Obstet Gynecol 73(2):418–421

    PubMed  CAS  Google Scholar 

  14. Moen MH (1994) Endometriosis in monozygotic twins. Acta Obstet Gynecol Scand 73(1):59–62

    Article  PubMed  CAS  Google Scholar 

  15. Kennedy S (2003) Genetics of endometriosis: a review of the positional cloning approaches. Semin Reprod Med 21(2):111–118

    Article  PubMed  Google Scholar 

  16. Hadfield RM et al (1997) Endometriosis in monozygotic twins. Fertil Steril 68(5):941–942

    Article  PubMed  CAS  Google Scholar 

  17. Treloar SA et al (1999) Genetic influences on endometriosis in an Australian twin sample. sueT@qimr.edu.au. Fertil Steril 71(4):701–710

    Article  PubMed  CAS  Google Scholar 

  18. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364(9447):1789–1799

    Article  PubMed  Google Scholar 

  19. Seli E, Berkkanoglu M, Arici A (2003) Pathogenesis of endometriosis. Obstet Gynecol Clin N Am 30(1):41–61

    Article  Google Scholar 

  20. dos Reis RM et al (1999) Familial risk among patients with endometriosis. J Assist Reprod Genet 16(9):500–503

    Article  PubMed  Google Scholar 

  21. Lamb KT (1986) National data registry for endometriosis. Wis Med J 85(8):27–28

    PubMed  CAS  Google Scholar 

  22. Kennedy S, Bennett S, Weeks DE (2001) Affected sib-pair analysis in endometriosis. Hum Reprod Update 7(4):411–418

    Article  PubMed  CAS  Google Scholar 

  23. Bischoff FZ, Simpson JL (2000) Heritability and molecular genetic studies of endometriosis. Hum Reprod Update 6(1):37–44

    Article  PubMed  CAS  Google Scholar 

  24. Nakago S et al (2001) Association between endometriosis and N-acetyl transferase 2 polymorphisms in a UK population. Mol Hum Reprod 7(11):1079–1083

    Article  PubMed  CAS  Google Scholar 

  25. Baxter SW, Thomas EJ, Campbell IG (2001) GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer. Carcinogenesis 22(1):63–65

    Article  PubMed  CAS  Google Scholar 

  26. Zondervan KT, Cardon LR, Kennedy SH (2002) What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 17(6):1415–1423

    Article  PubMed  Google Scholar 

  27. Wu CH et al (2012) Polymorphisms of dioxin receptor complex components and detoxification-related genes jointly confer susceptibility to advanced-stage endometriosis in the Taiwanese Han population. Am J Reprod Immunol 67(2):160–168

    Article  PubMed  CAS  Google Scholar 

  28. Cramer DW et al (1996) Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT). Mol Hum Reprod 2(3):149–152

    Article  PubMed  CAS  Google Scholar 

  29. Baranova H et al (1999) Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis. Mol Hum Reprod 5(7):636–641

    Article  PubMed  CAS  Google Scholar 

  30. Georgiou I et al (1999) Association of estrogen receptor gene polymorphisms with endometriosis. Fertil Steril 72(1):164–166

    Article  PubMed  CAS  Google Scholar 

  31. Hsieh YY et al (2001) Androgen receptor trinucleotide polymorphism in endometriosis. Fertil Steril 76(2):412–413

    Article  PubMed  CAS  Google Scholar 

  32. Kitawaki J et al (2001) Oestrogen receptor-alpha gene polymorphism is associated with endometriosis, adenomyosis and leiomyomata. Hum Reprod 16(1):51–55

    Article  PubMed  CAS  Google Scholar 

  33. Chang CC et al (2002) The proline form of p53 codon 72 polymorphism is associated with endometriosis. Fertil Steril 77(1):43–45

    Article  PubMed  Google Scholar 

  34. Kado N et al (2002) Association of the CYP17 gene and CYP19 gene polymorphisms with risk of endometriosis in Japanese women. Hum Reprod 17(4):897–902

    Article  PubMed  CAS  Google Scholar 

  35. Wieser F et al (2003) Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing. J Soc Gynecol Investig 10(1):32–36

    Article  PubMed  CAS  Google Scholar 

  36. Fujimoto J et al (1999) Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata. Mol Hum Reprod 5(8):742–747

    Article  PubMed  CAS  Google Scholar 

  37. Luisi S et al (2006) Estrogen receptor gene polymorphisms are associated with recurrence of endometriosis. Fertil Steril 85(3):764–766

    Article  PubMed  CAS  Google Scholar 

  38. Kim SH et al (2005) Estrogen receptor dinucleotide repeat polymorphism is associated with minimal or mild endometriosis. Fertil Steril 84(3):774–777

    Article  PubMed  CAS  Google Scholar 

  39. Renner SP et al (2006) Evaluation of clinical parameters and estrogen receptor alpha gene polymorphisms for patients with endometriosis. Reproduction 131(1):153–161

    Article  PubMed  CAS  Google Scholar 

  40. Kajihara H et al (2011) New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal. Gynecol Endocrinol 27(2):73–79

    Article  PubMed  Google Scholar 

  41. Latha M et al (2011) Molecular pathogenesis of endometriosis; Toll-like receptor-4 A896G (D299G) polymorphism: a novel explanation. Genet Test Mol Biomark 15(3):181–184

    Article  CAS  Google Scholar 

  42. Han YJ et al (2009) Haplotype analysis of the matrix metalloproteinase-9 gene associated with advanced-stage endometriosis. Fertil Steril 91(6):2324–2330

    Article  PubMed  CAS  Google Scholar 

  43. Borghese B et al (2008) Genetic polymorphisms of matrix metalloproteinase 12 and 13 genes are implicated in endometriosis progression. Hum Reprod 23(5):1207–1213

    Article  PubMed  CAS  Google Scholar 

  44. Munksgaard PS, Blaakaer J (2012) The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol Oncol 124(1):164–169

    Article  PubMed  CAS  Google Scholar 

  45. Martini M et al (2002) Possible involvement of hMLH1, p16(INK4a) and PTEN in the malignant transformation of endometriosis. Int J Cancer 102(4):398–406

    Article  PubMed  CAS  Google Scholar 

  46. Kobayashi H et al (2009) Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review). Oncol Rep 22(2):233–240

    PubMed  CAS  Google Scholar 

  47. Vestergaard AL et al (2011) Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis. Mol Hum Reprod 17(12):758–761

    Article  PubMed  CAS  Google Scholar 

  48. Barbieri RL et al (1986) Elevated serum concentrations of CA-125 in patients with advanced endometriosis. Fertil Steril 45(5):630–634

    PubMed  CAS  Google Scholar 

  49. Abrao MS et al (1997) The use of biochemical markers in the diagnosis of pelvic endometriosis. Hum Reprod 12(11):2523–2527

    Article  PubMed  CAS  Google Scholar 

  50. Koninckx PR, Kennedy SH, Barlow DH (1998) Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update 4(5):741–751

    Article  PubMed  CAS  Google Scholar 

  51. Vercellini P et al (2011) ‘Waiting for Godot’: a commonsense approach to the medical treatment of endometriosis. Hum Reprod 26(1):3–13

    Article  PubMed  Google Scholar 

  52. Vincent K (2011) Pelvic pain in women: clinical and scientific aspects. Curr Opin Support Palliat Care 5(2):143–149

    Article  PubMed  Google Scholar 

  53. Fasciani A et al (2003) Three-dimensional in vitro culture of endometrial explants mimics the early stages of endometriosis. Fertil Steril 80(5):1137–1143

    Article  PubMed  Google Scholar 

  54. Osuga Y et al (2011) Lymphocytes in endometriosis. Am J Reprod Immunol 65(1):1–10

    Article  PubMed  Google Scholar 

  55. Berbic M, Fraser IS (2011) Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. J Reprod Immunol 88(2):149–155

    Article  PubMed  CAS  Google Scholar 

  56. Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z (2011) Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem 18(2):200–208

    Article  PubMed  CAS  Google Scholar 

  57. Gonzalez-Ramos R et al (2010) Involvement of the nuclear factor-kappaB pathway in the pathogenesis of endometriosis. Fertil Steril 94(6):1985–1994

    Article  PubMed  CAS  Google Scholar 

  58. Barrier BF (2010) Immunology of endometriosis. Clin Obstet Gynecol 53(2):397–402

    Article  PubMed  Google Scholar 

  59. Mathur SP (2000) Autoimmunity in endometriosis: relevance to infertility. Am J Reprod Immunol 44(2):89–95

    Article  PubMed  CAS  Google Scholar 

  60. Nielsen NM et al (2011) The co-occurrence of endometriosis with multiple sclerosis, systemic lupus erythematosus and Sjogren syndrome. Hum Reprod 26(6):1555–1559

    Article  PubMed  Google Scholar 

  61. Petta CA et al (2007) Thyroid autoimmunity and thyroid dysfunction in women with endometriosis. Hum Reprod 22(10):2693–2697

    Article  PubMed  CAS  Google Scholar 

  62. de Ziegler D, Borghese B, Chapron C (2010) Endometriosis and infertility: pathophysiology and management. Lancet 376(9742):730–738

    Article  PubMed  Google Scholar 

  63. Sarapik A et al (2010) Serum anti-endometrial antibodies in infertile women-potential risk factor for implantation failure. Am J Reprod Immunol 63(5):349–357

    Article  PubMed  CAS  Google Scholar 

  64. Herington JL et al (2011) Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. Fertil Steril 95(4):1295.e1–1301.e1

    Article  Google Scholar 

  65. Zorio E et al (2008) Fibrinolysis: the key to new pathogenetic mechanisms. Curr Med Chem 15(9):923–929

    Article  PubMed  CAS  Google Scholar 

  66. diZerega GS, Campeau JD (2001) Peritoneal repair and post-surgical adhesion formation. Hum Reprod Update 7(6):547–555

    Article  PubMed  CAS  Google Scholar 

  67. Hellebrekers BW et al (2005) A role for the fibrinolytic system in postsurgical adhesion formation. Fertil Steril 83(1):122–129

    Article  PubMed  Google Scholar 

  68. Mohamed AM et al (2011) Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis. Eur J Obstet Gynecol Reprod Biol 156(2):177–180

    Article  PubMed  Google Scholar 

  69. Goncalves-Filho RP et al (2011) Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis. Acta Obstet Gynecol Scand 90(5):473–477

    Article  PubMed  CAS  Google Scholar 

  70. Tsukahara H (2007) Biomarkers for oxidative stress: clinical application in pediatric medicine. Curr Med Chem 14(3):339–351

    Article  PubMed  CAS  Google Scholar 

  71. Alpay Z, Saed GM, Diamond MP (2006) Female infertility and free radicals: potential role in adhesions and endometriosis. J Soc Gynecol Investig 13(6):390–398

    Article  PubMed  CAS  Google Scholar 

  72. Lambrinoudaki IV et al (2009) Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril 91(1):46–50

    Article  PubMed  CAS  Google Scholar 

  73. Ishikawa M (1993) Oxygen radicals-superoxide dismutase system and reproduction medicine. Nihon Sanka Fujinka Gakkai Zasshi 45(8):842–848

    PubMed  CAS  Google Scholar 

  74. Murphy AA et al (1998) Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis. Fertil Steril 69(6):1092–1094

    Article  PubMed  CAS  Google Scholar 

  75. Defrere S et al (2011) Insights into iron and nuclear factor-kappa B (NF-kappaB) involvement in chronic inflammatory processes in peritoneal endometriosis. Histol Histopathol 26(8):1083–1092

    PubMed  CAS  Google Scholar 

  76. Bruner-Tran KL et al (2008) Dioxin may promote inflammation-related development of endometriosis. Fertil Steril 89(5 Suppl):1287–1298

    Article  PubMed  CAS  Google Scholar 

  77. Verit FF, Erel O, Celik N (2008) Serum paraoxonase-1 activity in women with endometriosis and its relationship with the stage of the disease. Hum Reprod 23(1):100–104

    Article  PubMed  CAS  Google Scholar 

  78. Polak G et al (2011) Increased oxidized LDL cholesterol levels in peritoneal fluid of women with advanced-stage endometriosis. Ginekol Pol 82(3):191–194

    PubMed  Google Scholar 

  79. Mier-Cabrera J et al (2008) Effect of vitamins C and E supplementation on peripheral oxidative stress markers and pregnancy rate in women with endometriosis. Int J Gynaecol Obstet 100(3):252–256

    Article  PubMed  CAS  Google Scholar 

  80. Mier-Cabrera J et al (2009) Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet. Reprod Biol Endocrinol 7:54

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Augoulea.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Augoulea, A., Alexandrou, A., Creatsa, M. et al. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Arch Gynecol Obstet 286, 99–103 (2012). https://doi.org/10.1007/s00404-012-2357-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-012-2357-8

Keywords

Navigation