Skip to main content

Advertisement

SpringerLink
Log in

Reduced Levels of Serum Pigment Epithelium-Derived Factor in Women With Endometriosis

  • Original Articles
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The authors previously demonstrated decreased levels of pigment epithelium-derived factor (PEDF) in peritoneal fluid of women with endometriosis compared to women without endometriosis. Here, the authors determine whether women with endometriosis have altered levels of PEDF in serum. Peripheral blood samples were collected from 71 women with and without endometriosis (n = 43 and 28, respectively) before laparoscopic surgery. Concentrations of serum PEDF were measured by enzyme-linked immunosorbent assay. We detected lower levels of serum PEDF in women with endometriosis (16.3 ± 6.6 ng/mL) than in those without endometriosis (24.5 ± 7.3 ng/mL; P < .001). In women with endometriosis, the concentrations of serum PEDF were significantly lower in women with pain (n = 11, 12.6 ± 7.1 ng/mL) compared to women without pain (n = 32, 17.5 ± 6.0 ng/mL; P < .05). However, the concentrations of serum PEDF did not correlate with disease stage or site or infertility. In addition, the concentrations of serum PEDF did not show any difference in the phase of the cycle in either group. Our results suggest that reduced levels of serum PEDF in women with endometriosis and disease-related pain may play a role in the pathogenesis of this disease.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zhang X, Lin J, Qian Y, Deng L. Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis. Fertil Steril. 2004;81(5):1229–1234.

    Article  CAS  PubMed  Google Scholar 

  2. Xu H, Lui WT, Chu CY, Ng PS, Wang CC, Rogers MS. Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model. Hum Reprod. 2009;24(3):608–618.

    Article  CAS  PubMed  Google Scholar 

  3. Cosín R, Gilabert-Estellés J, Ramón LA, et al. Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis. Hum Reprod. 2010;25(2):398–405.

    Article  PubMed  CAS  Google Scholar 

  4. Fujii EY, Nakayama M, Nakagawa A. Concentrations of receptor for advanced glycation end products, VEGF and CML in plasma, follicular fluid, and peritoneal fluid in women with and without endometriosis. Reprod Sci. 2008;15(10):1066–1074.

    Article  CAS  PubMed  Google Scholar 

  5. Cho SH, Oh YJ, Nam A, et al. Evaluation of serum and urinary angiogenic factors in patients with endometriosis. Am J Reprod Immunol. 2007;58(6):497–504.

    Article  CAS  PubMed  Google Scholar 

  6. Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K, Hornung D. Combination of CCR1 mRNA, MCP1, and CA125 measurements in peripheral blood as a diagnostic test for endometriosis. Reprod Sci. 2008;15(9):906–911.

    Article  PubMed  Google Scholar 

  7. Chae SJ, Kim H, Jee BC, Suh CS, Kim SH, Kim JG. Tumor necrosis factor (TNF)-TNF receptor gene polymorphisms and their serum levels in Korean women with endometriosis. Am J Reprod Immunol. 2008;60(5):432–439.

    Article  CAS  PubMed  Google Scholar 

  8. Ohata Y, Harada T, Miyakoda H, Taniguchi F, Iwabe T, Terakawa N. Serum interleukin-8 levels are elevated in patients with ovarian endometrioma. Fertil Steril. 2008;90(4):994–999.

    Article  CAS  PubMed  Google Scholar 

  9. Bourlev V, Iljasova N, Adamyan L, Larsson A, Olovsson M. Signs of reduced angiogenic activity after surgical removal of deeply infiltrating endometriosis. Fertil Steril. 2010;94(1): 52–57.

    Article  CAS  PubMed  Google Scholar 

  10. Machado DE, Berardo PT, Palmero CY, Nasciutti LE. Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases. J Exp Clin Cancer Res. 2010;29:4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Machado DE, Berardo PT, Palmero CY, Nasciutti LE. A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model. Fertil Steril. 2010; 93(8):2674–2679.

    Article  CAS  PubMed  Google Scholar 

  12. Di Carlo C, Bonifacio M, Tommaselli GA, Bifulco G, Guerra G, Nappi C. Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium. Fertil Steril. 2009;91(6):2315–2323.

    Article  PubMed  CAS  Google Scholar 

  13. Becker CM, D’Amato RJ. Angiogenesis and antiangiogenic therapy in endometriosis. Microvasc Res. 2007;74(2–3):121–130.

    Article  CAS  PubMed  Google Scholar 

  14. Tombran-Tink J, Chader GG, Johnson LV. PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res. 1991;53(3):411–414.

    Article  CAS  PubMed  Google Scholar 

  15. Hoshina D, Abe R, Yamagishi SI, Shimizu H. The role of PEDF in tumor growth and metastasis. Curr Mol Med. 2010;10(3): 292–295.

    Article  CAS  PubMed  Google Scholar 

  16. Yamagishi S, Adachi H, Abe A, et al. Elevated serum levels of pigment epithelium-derived factor in the metabolic syndrome. J Clin Endocrinol Metab. 2006;91(6):2447–2450.

    Article  CAS  PubMed  Google Scholar 

  17. Yamagishi S, Matsui T, Takenaka K, Nakamura K, Takeuchi M, Hiroyoshi Inoue H. Pigment epithelium-derived factor (PEDF) prevents platelet activation and aggregation in diabetic rats by blocking deleterious effects of advanced glycation end products (AGEs). Diabetes Metab Res Rev. 2009;25(3): 266–271.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang T, Guan M, Xu C, Chen Y, Lu Y. Pigment epithelium-derived factor inhibits glioma cell growth in vitro and in vivo. Life Sci. 2007; 81(16):1256–1263.

    Article  CAS  PubMed  Google Scholar 

  19. Broadhead ML, Dass CR, Choong PF. In vitro and in vivo biological activity of PEDF against a range of tumors. Expert Opin Ther Targets. 2009;13(12):1429–1438.

    Article  CAS  PubMed  Google Scholar 

  20. Ek ET, Dass CR, Choong PF. Pigment epithelium-derived factor: a multimodal tumor inhibitor. Mol Cancer Ther. 2006;5(7): 1641–1646.

    Article  CAS  PubMed  Google Scholar 

  21. Wang JJ, Zhang SX, Mott R, et al. Anti-inflammatory effects of pigment epithelium-derived factor in diabetic nephropathy. Am J Physiol Renal Physiol. 2008;294(5):F1166–F1173.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang SX, Wang JJ, Dashti A, et al. Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein. J Mol Endocrinol. 2008;41(3):135–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang H, Cheng R, Liu G, et al. PEDF inhibits growth of retinoblastoma by anti-angiogenic activity. Cancer Sci. 2009;100(12): 2419–2425.

    Article  CAS  PubMed  Google Scholar 

  24. Yang LP, Cheng P, Peng XC, et al. Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma. J Exp Clin Cancer Res. 2009;28:75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lin J, Zhang X, Chen Y. Mutagen sensitivity as a susceptibility marker for endometriosis. Hum Reprod. 2003;18(10):2052–2057.

    Article  PubMed  Google Scholar 

  26. Grammatikakis I, Zervoudis S, Evangelinakis N, Tziortzioti V. Endometrium and ovarian cancer synchronous to endometriosis—a retrospective study of our experience of 7 years. J Med Life. 2010;3(1):76–79.

    PubMed  PubMed Central  Google Scholar 

  27. Chen L, Fan R, Huang X, Xu H, Zhang X. Decreased concentrations of pigment epithelium-derived factor in peritoneal fluid of patients with endometriosis. Fertil Steril. 2011;95(5): 1798–1800.

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  29. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.

    Article  PubMed  Google Scholar 

  30. Becker CM, Wright RD, Satchi-Fainaro R, et al. A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy. Am J Pathol. 2006;168(6):2074–2084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hur SE, Lee JY, Moon HS, Chung HW. Angiopoietin-1, angiopoietin-2 and Tie-2 expression in eutopic endometrium in advanced endometriosis. Mol Hum Reprod. 2006;12(7):421–426.

    Article  CAS  PubMed  Google Scholar 

  32. Matsuzaki S, Murakami T, Uehara S, et al. Erythropoietin concentrations are elevated in the peritoneal fluid of women with endometriosis. Hum Reprod. 2001;16(5):945–948.

    Article  CAS  PubMed  Google Scholar 

  33. Elayappan B, Ravinarayannan H, Pasha SP, Lee KJ, Gurunathan S. PEDF inhibits VEGF- and EPO-induced angiogenesis in retinal endothelial cells through interruption of PI3K/Akt phosphorylation. Angiogenesis. 2009;12(4):313–324.

    Article  CAS  PubMed  Google Scholar 

  34. Haribalaganesh R, Sheikpranbabu S, Banumathi E, Gurunathan S. Pigment epithelium-derived factor inhibits erythropoietin-induced retinal endothelial cell angiogenesis by suppression of PI3K/Akt pathway. Exp Eye Res. 2010;90(6):726–733.

    Article  CAS  PubMed  Google Scholar 

  35. Sheikpranbabu S, Ravinarayanan H, Elayappan B, Jongsun P, Gurunathan S. Pigment epithelium-derived factor inhibits vascular endothelial growth factor-and interleukin-1beta-induced vascular permeability and angiogenesis in retinal endothelial cells. Vascul Pharmacol. 2010;52(1–2):84–94.

    Article  CAS  PubMed  Google Scholar 

  36. Tan ML, Choong PF, Dass CR. Anti-chondrosarcoma effects of PEDF mediated via molecules important to apoptosis, cell cycling, adhesion and invasion. Biochem Biophys Res Commun. 2010;398(4):613–618.

    Article  CAS  PubMed  Google Scholar 

  37. Barrier BF, Sharpe-Timms KL. Expression of soluble adhesion molecules in sera of women with stage III and IV endometriosis. J Soc Gynecol Investigl. 2002;9(2):98–101.

    Article  CAS  Google Scholar 

  38. Gmyrek GB, Sozanski R, Jerzak M, et al. Evaluation of monocyte chemotactic protein-1 levels in peripheral blood of infertile women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2005;122(2):199–205.

    Article  CAS  PubMed  Google Scholar 

  39. Podgaec S, Dias Junior JA, Chapron C, Oliveira RM, Baracat EC, Abrão MS. Th1 and Th2 immune responses related to pelvic endometriosis. Rev Assoc Med Bras. 2010;56(1):92–98.

    Article  PubMed  Google Scholar 

  40. Lambrinoudaki IV, Augoulea A, Christodoulakos GE, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril. 2009;91(1):46–50.

    Article  CAS  PubMed  Google Scholar 

  41. Jackson LW, Schisterman EF, Dey-Rao R, Browne R, Armstrong D. Oxidative stress and endometriosis. Hum Reprod. 2005;20(7): 2014–2020.

    Article  CAS  PubMed  Google Scholar 

  42. Ek ET, Dass CR, Contreras KG, Choong PF. PEDF-derived synthetic peptides exhibit antitumor activity in an orthotopic model of human osteosarcoma. J Orthop Res. 2007;25(12):1671–1680.

    Article  CAS  PubMed  Google Scholar 

  43. Dass CR, Ek ET, Choong PF. PEDF as an emerging therapeutic candidate for osteosarcoma. Curr Cancer Drug Targets. 2008; 8(8):683–690.

    Article  CAS  PubMed  Google Scholar 

  44. Palmieri D, Watson JM, Rinehart CA. Age-related expression of PEDF/EPC-1 in human endometrial stromal fibroblasts: implications for interactive senescence. Exp Cell Res. 1999; 247(1):142–147.

    Article  CAS  PubMed  Google Scholar 

  45. Cheung LW, Au SC, Cheung AN, et al. Pigment epithelium-derived factor is estrogen sensitive and inhibits the growth of human ovarian cancer and ovarian surface epithelial cells. Endocrinology. 2006;147(9):4179–4191.

    Article  CAS  PubMed  Google Scholar 

  46. Stejskal D, Karpísek M, Svesták M, Hejduk P, Sporová L, Kotolová H. Pigment epithelium-derived factor as a new marker of metabolic syndrome in Caucasian population. J Clin Lab Anal. 2010;24(1):17–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ferrero S, Gillott DJ, Anserini P, et al. Vitamin D binding protein in endometriosis. J Soc Gynecol Investig. 2005;12(4):272–277.

    Article  CAS  PubMed  Google Scholar 

  48. Agic A, Xu H, Altgassen C, et al. Relative expression of 1, 25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod Sci. 2007; 14(5):486–497.

    Article  CAS  PubMed  Google Scholar 

  49. Pretta S, Remorgida V, Abbamonte LH, et al. Atherosclerosis in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2007;132(2):226–231.

    Article  PubMed  Google Scholar 

  50. Somigliana E, Panina-Bordignon P, Murone S, Di Lucia P, Vercellini P, Vigano P. Vitamin D reserve is higher in women with endometriosis. Hum Reprod. 2007;22(8):2273–2278.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. Kobayashi H, Yamada Y, Kanayama S, et al. The role of iron in the pathogenesis of endometriosis. Gynecol Endocrinol. 2009; 25(1):39–52.

    Article  CAS  PubMed  Google Scholar 

  53. Yamaguchi K, Mandai M, Oura T, et al. Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes. Oncogene. 2010; 29(12):1741–1752.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Women’s Hospital, Zhejiang University School of Medicine, 2 Xueshi Road, Hangzhou, Zhejiang, 310006, P. R. China

    Liqing Chen MD, Ruijia Fan MD, Xiufeng Huang MD, Hong Xu MD & Xinmei Zhang MD

Authors
  1. Liqing Chen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruijia Fan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiufeng Huang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xinmei Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xinmei Zhang MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, L., Fan, R., Huang, X. et al. Reduced Levels of Serum Pigment Epithelium-Derived Factor in Women With Endometriosis. Reprod. Sci. 19, 64–69 (2012). https://doi.org/10.1177/1933719111413300

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719111413300

Keywords

Search

Navigation