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

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. Similar content being viewed by others

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Becker CM, D’Amato RJ. Angiogenesis and antiangiogenic therapy in endometriosis. Microvasc Res. 2007;74(2–3):121–130. 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. 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. 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. 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. 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. 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. Ek ET, Dass CR, Choong PF. Pigment epithelium-derived factor: a multimodal tumor inhibitor. Mol Cancer Ther. 2006;5(7): 1641–1646. 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. 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. Yang H, Cheng R, Liu G, et al. PEDF inhibits growth of retinoblastoma by anti-angiogenic activity. Cancer Sci. 2009;100(12): 2419–2425. 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. Lin J, Zhang X, Chen Y. Mutagen sensitivity as a susceptibility marker for endometriosis. Hum Reprod. 2003;18(10):2052–2057. 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. 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. American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis 1996. Fertil Steril. 1997;67(5):817–821. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Jackson LW, Schisterman EF, Dey-Rao R, Browne R, Armstrong D. Oxidative stress and endometriosis. Hum Reprod. 2005;20(7): 2014–2020. 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. Dass CR, Ek ET, Choong PF. PEDF as an emerging therapeutic candidate for osteosarcoma. Curr Cancer Drug Targets. 2008; 8(8):683–690. 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. 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. 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. Ferrero S, Gillott DJ, Anserini P, et al. Vitamin D binding protein in endometriosis. J Soc Gynecol Investig. 2005;12(4):272–277. 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. Pretta S, Remorgida V, Abbamonte LH, et al. Atherosclerosis in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2007;132(2):226–231. 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. 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. Kobayashi H, Yamada Y, Kanayama S, et al. The role of iron in the pathogenesis of endometriosis. Gynecol Endocrinol. 2009; 25(1):39–52. 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. Author information Authors and Affiliations Corresponding author Rights 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 Published: Issue date: DOI: https://doi.org/10.1177/1933719111413300