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Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications

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Abstract

This study was undertaken to test the hypotheses that, due to gradual accumulation of dead erythrocytes and their ingested products resulting from repeated hemorrhage, older endometriomas (whitish in color) contain chocolate fluid with higher iron content than younger (brownish/blackish in color) ones with concomitant higher collagen content and more adhesions. We recruited 30 premenopausal women with histologically confirmed ovarian endometriomas and collected samples of their endometriotic lesions and chocolate fluid and measured the viscosity, density, and the concentration of total bilirubin, ferritin, and free iron of the chocolate fluid. We also evaluated the lesion color and adhesion scores. In addition, we performed Masson trichrome and Picro-Sirius red staining on all endometriotic cysts and evaluated the extent of fibrosis in the lesions. We found that fluids taken from white-colored endometriomas had significantly higher concentration of total bilirubin, ferritin, and free iron, respectively, than black/brown-colored ones. In addition, older cysts had fluids that had significantly higher density and viscosity. Fluid density correlated positively with the concentrations of total bilirubin, ferritin, and free iron. Older lesions had significantly more collagen content and higher adhesion scores. Taken together, these data supports the notion that older cysts, having experienced more bleeding episodes, contain chocolate fluid that is higher in viscosity, density, and iron content and higher fibrotic content than younger ones. This provides another piece of evidence that endometriotic lesions are wounds that undergo repeated injury and repair, resulting ultimately fibrotic lesions that are resistant to hormonal treatment.

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References

  1. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–596.

    Article  CAS  PubMed  Google Scholar 

  2. Vercellini P. Endometriosis: what a pain it is. Semin Reprod Endocrinol. 1997;15(3):251–261.

    Article  CAS  PubMed  Google Scholar 

  3. Sampson JA. Perforating hemorrhagic (chocolate) cysts of the ovary. Tr Am Gynec Soc. 1921;46(1):162–236.

    Google Scholar 

  4. Martin DC, Berry JD. Histology of chocolate cysts. J Gynecol Surg. 1990;6(1):43–46.

    Article  Google Scholar 

  5. Brosens IA, Puttemans PJ, Deprest J. The endoscopic localization of endometrial implants in the ovarian chocolate cyst. Fertil Steril. 1994;61(6):1034–1038.

    Article  CAS  PubMed  Google Scholar 

  6. Nezhat C, Nezhat F, Seidman DS. Classification of endometriosis. Improving the classification of endometriotic ovarian cysts. Hum Reprod. 1994;9(12):2212–2213.

    Article  CAS  PubMed  Google Scholar 

  7. Brosens IA, Puttemans P, Deprest J, Rombauts L. The endometriosis cycle and its derailments. Hum Reprod. 1994;9(5):770–1.

    Article  CAS  PubMed  Google Scholar 

  8. Busacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Curr Opin Obstet Gynecol. 2003; 15(4):321–326.

    PubMed  Google Scholar 

  9. Redwine DB. Age-related evolution in color appearance of endometriosis. Fertil Steril. 1987;48(8): 1062–1063.

    Article  CAS  PubMed  Google Scholar 

  10. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5): 817–821.

  11. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007; 22(1):266–71.

    Article  CAS  PubMed  Google Scholar 

  12. Liu X, Yuan L, Shen F, Zhu Z, Jiang H, Guo SW. Patterns of and risk factors for recurrence in women with ovarian endometriomas. Obstet Gynecol. 2007; 109(6): 1411–1420.

    Article  PubMed  Google Scholar 

  13. Nisolle M. Ovarian endometriosis and peritoneal endometriosis: are they different entities from a fertility perspective? Curr Opin Obstet Gynecol. 2002;14(3):283–288.

    Article  PubMed  Google Scholar 

  14. Friedman SL. Liver fibrosis—from bench to bedside. J Hepatol. 2003;38 Suppl 1:S38–S53.

    Article  PubMed  Google Scholar 

  15. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 2006;69(2):213–217.

    Article  CAS  PubMed  Google Scholar 

  16. Ding D, Liu X, Duan J, Guo SW. Platelets are a unindicted culprit in the development of endometriosis. Hum Reprod. In press.

  17. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199–210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Defrere S, Lousse JC, Gonzalez-Ramos R, Colette S, Donnez J, Van Langendonckt A. Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod. 2008; 14(7):377–385.

    Article  CAS  PubMed  Google Scholar 

  19. Theil EC. Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms. Annu Rev Biochem. 1987;56(1):289–315.

    Article  CAS  PubMed  Google Scholar 

  20. Iizuka M, Igarashi M, Abe Y, Ibuki Y, Koyasu Y, Ikuma K. Chemical assay of iron in ovarian cysts: a new diagnostic method to evaluate endometriotic cysts. Gynecol Obstet Invest. 1998; 46(1):58–60.

    Article  CAS  PubMed  Google Scholar 

  21. Yamaguchi K, Mandai M, Toyokuni S, et al. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the ironinduced persistent oxidative stress. Clin Cancer Res. 2008; 14(1):32–40.

    Article  CAS  PubMed  Google Scholar 

  22. Sugimura K, Takemori M, Sugiura M, Okizuka H, Kono M, Ishida T. The value of magnetic resonance relaxation time in staging ovarian endometrial cysts. Br J Radiol. 1992;65(774): 502–506.

    Article  CAS  PubMed  Google Scholar 

  23. Takahashi K, Okada S, Okada M, Kitao M, Kaji Y, Sugimura K. Magnetic resonance relaxation time in evaluating the cyst fluid characteristics of endometrioma. Hum Reprod. 1996; 11 (4): 857–860.

    Article  CAS  PubMed  Google Scholar 

  24. Arumugam K. Endometriosis and infertility: raised iron concentration in the peritoneal fluid and its effect on the acrosome reaction. Hum Reprod. 1994;9(6):1153–1157.

    Article  CAS  PubMed  Google Scholar 

  25. Arumugam K, Yip YC. De novo formation of adhesions in endometriosis: the role of iron and free radical reactions. Fertil Steril. 1995;64(1):62–64.

    Article  CAS  PubMed  Google Scholar 

  26. Van Langendonckt A, Casanas-Roux F, Dolmans MM, Donnez J. Potential involvement of hemoglobin and heme in the pathogenesis of peritoneal endometriosis. Fertil Steril. 2002;77(3): 561–570.

    Article  PubMed  Google Scholar 

  27. Lousse JC, Defrere S, Van Langendonckt A, et al. Iron storage is significantly increased in peritoneal macrophages of endometriosis patients and correlates with iron overload in peritoneal fluid. Fertil Steril. 2009;91(5):1668–1675.

    Article  PubMed  Google Scholar 

  28. Polak G, Wertel I, Tarkowski R, Morawska D, Nowakowski A, Kotarski J. Ferritin levels in the peritoneal fluid—a new endometriosis marker? [in Polish]. Ginekol Pol. 2006;77(5): 389–393.

    PubMed  Google Scholar 

  29. Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. Semin Thromb Hemost. 2003;29(5):435–450.

    Article  CAS  PubMed  Google Scholar 

  30. Junqueira LC, Bignolas G, Brentani RR. Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J. 1979;11(4):447–455.

    Article  CAS  PubMed  Google Scholar 

  31. Street JM, Souza AC, Alvarez-Prats A, et al. Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy. Physiol Rep. 2014; 2(7): pii: el2088.

    Article  Google Scholar 

  32. Team R. A language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2013.

    Google Scholar 

  33. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012;18(7):1028–1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rivlin ME, Krueger RP, Wiser WL. Danazol in the management of ureteral obstruction secondary to endometriosis. Fertil Steril. 1985;44(2):274–276.

    Article  CAS  PubMed  Google Scholar 

  35. Muzii L, Bianchi A, Bellati F, et al. Histologic analysis of endometriomas: what the surgeon needs to know. Fertil Steril. 2007; 87(2):362–366.

    Article  PubMed  Google Scholar 

  36. Sanchez AM, Vigano P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M. The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary. Hum Reprod Update. 2014;20(2):217–230

    Article  CAS  PubMed  Google Scholar 

  37. Van Langendonckt A, Casanas-Roux F, Donnez J. Iron overload in the peritoneal cavity of women with pelvic endometriosis. Fertil Steril. 2002;78(4):712–718.

    Article  PubMed  Google Scholar 

  38. Defrere S, Van Langendonckt A, Vaesen S, et al. Iron overload enhances epithelial cell proliferation in endometriotic lesions induced in a murine model. Hum Reprod. 2006;21(11):2810–2816.

    Article  CAS  PubMed  Google Scholar 

  39. Guo SW. Nuclear factor-kappab (NF-kappaB): an unsuspected major culprit in the pathogenesis of endometriosis that is still at large? Gynecol Obstet Invest. 2007;63(2):71–97.

    Article  CAS  PubMed  Google Scholar 

  40. Gonzalez-Ramos R, Donnez J, Defrere S, et al. Nuclear factorkappa B is constitutively activated in peritoneal endometriosis. Mol Hum Reprod. 2007;13(7):503–509.

    Article  CAS  PubMed  Google Scholar 

  41. Gonzalez-Ramos R, Van Langendonckt A, Defrere S, et al. Involvement of the nuclear factor-kappaB pathway in the pathogenesis of endometriosis. Fertil Steril. 2010;94(6): 1985–1994.

    Article  CAS  PubMed  Google Scholar 

  42. Delima RD, Chua AC, Tirnitz-Parker JE, et al. Disruption of hemochromatosis protein and transferrin receptor 2 causes ironinduced liver injury in mice. Hepatology. 2012;56(2):585–593.

    Article  CAS  PubMed  Google Scholar 

  43. Zakynthinos E, Vassilakopoulos T, Kaltsas P, et al. Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major. Thorax. 2001;56(9):737–739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sampaio AF, Silva M, Dornas WC, et al. Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes. Biometals. 2014;27(2):349–361.

    Article  CAS  PubMed  Google Scholar 

  45. Walter AJ, Hentz JG, Magtibay PM, Cornelia JL, Magrina JF. Endometriosis: correlation between histologic and visual findings at laparoscopy. Am J Obstet Gynecol. 2001;184(7):1407–1411.

    Article  CAS  PubMed  Google Scholar 

  46. Stripling MC, Martin DC, Chatman DL, Zwaag RV, Poston WM. Subtle appearance of pelvic endometriosis. Fertil Steril. 1988; 49(3):427–431.

    Article  CAS  PubMed  Google Scholar 

  47. Wykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: a systematic quantitative review. BJOG. 2004;111(11):1204–1212.

    Article  PubMed  Google Scholar 

  48. Stratton P, Winkel CA, Sinaii N, Merino MJ, Zimmer C, Nieman LK. Location, color, size, depth, and volume may predict endometriosis in lesions resected at surgery. Fertil Steril. 2002;78(4):743–749.

    Article  PubMed  Google Scholar 

  49. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13(6): 1686–1690.

    Article  CAS  PubMed  Google Scholar 

  50. Van Langendonckt A, Eggermont J, Casanas-Roux F, Scholtes HE, Donnez J. Expression of platelet endothelial cell adhesion molecule-1 in red and black endometriotic lesions. Fertil Steril. 2004;82(4):984–985.

    Article  PubMed  Google Scholar 

  51. Willems S, Verleden SE, Vanaudenaerde BM, et al. Multiplex protein profiling of bronchoalveolar lavage in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis. Ann Thorac Med. 2013;8(1):38–45.

    Article  CAS  PubMed  Google Scholar 

  52. Colwell AS, Beanes SR, Soo C, et al. Increased angiogenesis and expression of vascular endothelial growth factor during scarless repair. Plast Reconstr Surg. 2005;115(1):204–212.

    CAS  PubMed  Google Scholar 

  53. Lian YG, Zhou QG, Zhang YJ, Zheng FL. VEGF ameliorates tubulointerstitial fibrosis in unilateral ureteral obstruction mice via inhibition of epithelial-mesenchymal transition. Acta Pharmacol Sin. 2011;32(12):1513–1521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hong JP, Li XM, Li MX, Zheng FL. VEGF suppresses epithelialmesenchymal transition by inhibiting the expression of Smad3 and miR192, a Smad3-dependent microRNA. Int J Mol Med. 2013;31(6):1436–1442.

    Article  CAS  PubMed  Google Scholar 

  55. Matsuzaki S, Darcha C. Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod. 2012;27(3):712–721.

    Article  CAS  PubMed  Google Scholar 

  56. Matsuzaki S, Darcha C. Involvement of the wnt/beta-catenin signaling pathway in the cellular and molecular mechanisms of fibrosis in endometriosis. PIoS One. 2013; 8(10):e76808.

    Article  CAS  Google Scholar 

  57. Rhyu DY, Yang Y, Ha H, et al. Role of reactive oxygen species in TGF-betal-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol. 2005;16(3):667–675.

    Article  CAS  PubMed  Google Scholar 

  58. Radisky DC, Levy DD, Littlepage LE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 2005;436(7047):123–127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fukunaga M. Smooth muscle metaplasia in ovarian endometriosis. Histopathology. 2000;36(4):348–352.

    Article  CAS  PubMed  Google Scholar 

  60. Mechsner S, Bartley J, Loddenkemper C, Salomon DS, Starzinski-Powitz A, Ebert AD. Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril. 2005;83 Suppl 1:1220–1231.

    Article  CAS  PubMed  Google Scholar 

  61. Odagiri K, Konno R, Fujiwara H, Netsu S, Yang C, Suzuki M. Smooth muscle metaplasia and innervation in interstitium of endometriotic lesions related to pain. Fertil Steril. 2009;92(5): 1525–1531.

    Article  PubMed  Google Scholar 

  62. Boss EA, Massuger LF, Thomas CM, et al. Clinical value of components of the plasminogen activation system in ovarian cyst fluid. Anticancer Res. 2002;22(1A):275–282.

    CAS  PubMed  Google Scholar 

  63. Ghosh AK, Vaughan DE. PAI-1 in tissue fibrosis. J Cell Physiol. 2012;227(2):493–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Roberts CP, Rock JA. The current staging system for endometriosis: does it help? Obstet Gynecol Clin North Am. 2003;30(1): 115–132.

    Article  PubMed  Google Scholar 

  65. Adamson GD. Endometriosis classification: an update. Curr Opin Obstet Gynecol. 2011;23(4):213–220.

    Article  PubMed  Google Scholar 

  66. Gonzalez-Quintero VH, Cruz-Pachano FE. Preventing adhesions in obstetric and gynecologic surgical procedures. Rev Obstet Gynecol. 2009;2(1):38–45.

    PubMed  PubMed Central  Google Scholar 

  67. Alpay Z, Saed GM, Diamond MP. Postoperative adhesions: from formation to prevention. Semin Reprod Med. 2008;26(4):313–321.

    Article  CAS  PubMed  Google Scholar 

  68. Vercellini P, Aimi G, Panazza S, Vicentini S, Pisacreta A, Crosignani PG. Deep endometriosis conundrum: evidence in favor of a peritoneal origin. Fertil Steril. 2000;73(5): 1043–1046.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Shanghai Obstetrics and Gynecology Hospital, Fudan University Shanghai College of Medicine, 419 Fangxie Road, 200011, Shanghai, China

    Sun-Wei Guo PhD, Ding Ding MD, PhD, Minhong Shen MD & Xishi Liu MD, PhD

  2. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China

    Sun-Wei Guo PhD & Xishi Liu MD, PhD

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  1. Sun-Wei Guo PhD
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  2. Ding Ding MD, PhD
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Guo, SW., Ding, D., Shen, M. et al. Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications. Reprod. Sci. 22, 873–883 (2015). https://doi.org/10.1177/1933719115570907

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