Endometriosis and Oxidative Stress

Endometriosis is a chronic gynecologic disease process with multifactorial etiology. Increased oxidative stress, a result of increased production of free radicals or depletion of the body’s endogenous antioxidant defense, has been implicated in its pathogenesis. Oxidative stress is thought to promote angiogenesis and the growth and proliferation of endometriotic implants. Oxidative stress in the reproductive tract microenvironment is known to negatively affect sperm count and quality and may also arrest fertilized egg division leading to embryo death. Increased DNA damage in sperm, oocytes, and resultant embryos may account for the increase in miscarriages and fertilization and implantation failures seen in patients with endometriosis. The evidence linking endometriosis and infertility to endogenous pro-oxidant imbalance provides a rationale for the empiric use of antioxidant therapy. Vitamin C and E deficiency has been demonstrated in women with endometriosis. Observational and randomized controlled studies have shown vitamin C and E combination therapy to decrease markers of oxidative stress. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

Snesky TE, Liu DT (1980) Endometriosis: associations with menorrhagia, infertility, and oral contraceptives. Int J Gynaecol Obstet 17:573–576 Cramer DW (1987) Epidemiology of endometriosis in adolescents. In: Wilson EA (ed) Endometriosis, vol 1. Alan Liss, New York, pp 5–8 Giudice L, Kao L (2004) Endometriosis. Lancet 364:1789–1799 Koninckx PR (1999) The physiopathology of endometriosis: pollution and dioxin. Gynecol Obstet Invest 47:47–49 Donnez J, Chantraine F, Nisolle M (2002) The efficacy of medical and surgical treatment of endometriosis-associated infertility: arguments in favour of a medico-surgical approach. Hum Reprod Update 8:89–94 Nisolle M, Donnez J (1997) Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 68:585–596 Van Langendonckt A, Casanas-Roux F, Dolmans MM, Donnez J (2002) Potential involvement of hemoglobin and heme in the pathogenesis of peritoneal endometriosis. Fertil Steril 77:561–570 Heilier JF, Donnez J, Lison D (2008) Organochlorines and endometriosis: a mini-review. Chemosphere 71:203–210 Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 64:151–154 Nap AW, Groothuis PG, Demir AY, Evers JL, Dunselman GA (2004) Pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol 18:233–244 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 Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, Fujii S (2008) Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Hum Cancer Biol 14(1):32–40 Templeton DM, Liu Y (2003) Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta 1619:113–124 Lachapelle MH, Hemmings R, Roy DC, Falcone T, Miron P (1996) Flow cytometric evaluation of leukocyte subpopulations in the follicular fluids of infertile patients. Fertil Steril 65:1135–1140 Seli E, Arici A (2003) Endometriosis: interaction of immune and endocrine systems. Semin Reprod Med 21:135–144 Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C (1998) The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 70:425–431 Garrido N, Navarro J, Remohi J, Simon C, Pellicer A (2000) Follicular hormonal environment and embryo quality in women with endometriosis. Hum Reprod Update 6:67–74 Wunder DM, Mueller MD, Birkhauser MH, Bersinger NA (2006) Increased ENA-78 in the follicular fluid of patients with endometriosis. Acta Obstet Gynecol Scand 85:336–342 Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A (2002) Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 17:426–431 Darai E, Detchev R, Hugol D, Quang NT (2003) Serum and cyst fluid levels of interleukin (IL) -6, IL-8 and tumour necrosis factor-alpha in women with endometriomas and benign and malignant cystic ovarian tumours. Hum Reprod 18:1681–1685 Ulukus M, Ulukus EC, Seval Y, Zheng W, Arici A (2005) Expression of interleukin-8 receptors in endometriosis. Hum Reprod 20:794–801 Agarwal A, Gupta S (2005) Role of reactive oxygen species in female reproduction. Part I. Oxidative stress: a general overview. Women Health 1:21–25 de Lamirande E, Gagnon C (1995) Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod 10:15–21 Alul RH, Wood M, Longo J, Marcotte AL, Campione AL, Moore MK, Lynch SM (2003) Vitamin C protects low-density lipoproteins from homocysteine-mediated oxidation. Free Radic Biol Med 34(7):881–891 Olek RA, Ziolkowski W, Kaczor JJ, Greci L, Popinigis J, Antosiewicz J (2004) Antioxidant activity of NADH and its analogue––an in vivo study. J Biochem Mol Biol 37:416–421 Reubinoff BE, Har-El R, Kitrossky N, Friedler S, Levi R, Lewin A, Chevion M (1996) Increased levels of redox-active iron in follicular fluid: a possible cause of free radical mediated infertility in beta-thalassemia major. Am J Obstet Gynecol 174(3):914–918 Arumugam K, Yip YC (1995) De novo formation of adhesions in endometriosis: the role of iron and free radical reactions. Fertil Steril 64(1):62–64 Murphy AA, Palinski W, Rankin S, Morales AJ, Parthasarathy S (1998) Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis. Fertil Steril 69(6):1092–1094 Donnez J, Van Langendonckt A, Casanas-Roux F et al (2002) Current thinking on the pathogenesis of endometriosis. Gynecol Obstet Invest 54(Suppl 1):52–58. Discussion 9–62 Foyouzi N, Berkkanoglu M, Arici A, Kwintkiewicz J, Izquierdo D, Duleba AJ (2004) Effects of oxidants and antioxidants on proliferation of endometrial stromal cells. Fertil Steril 82(3):1019–1022 Park JK, Song M, Dominguez CE, Walter MF, Santanam N, Parthasarathy S, Murphy AA (2006) Glycodelin mediates the increase in vascular endothelial growth factor in response to oxidative stress in the endometrium. Am J Obstet Gynecol 195(6):1772–1777 Wu Y, Kajdacsy-Balla A, Strawn E, Basir Z, Halverson G, Jailwala P, Wang Y, Wang X, Ghosh S, Guo SW (2006) Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology 147(1):232–246 Seo SK, Yang HI, Lee KE, Kim HY, Cho S, Choi YS, Lee BS (2010) The roles of thioredoxin and thioredoxin-binding protein-2 in endometriosis. Hum Reprod 25(5):1251–1258 Zeller JM, Henig I, Radwanska E, Dmowski WP (1987) Enhancement of human monocyte and peritoneal macrophage chemiluminescence activities in women with endometriosis. Am J Reprod Immunol Microbiol 13:78–82 Ota H, Igarashi S, Tanaka T (2001) Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril 75:785–790 Saito H, Seino T, Kaneko T, Nakahara K, Toya M, Kurachi H (2002) Endometriosis and oocyte quality. Gynecol Obstet Invest 53(1):46–51 Szczepanska M, Kozlik J, Skrzypczak J, Mikolajczyk M (2003) Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril 79:1288–1293 Gupta S, Agarwal A, Krajcir N, Alvarez JG (2006) Role of oxidative stress in endometriosis. Reprod Biomed Online 13(1):126–134 Polak G, Koziol-Montewka M, Gogacz M, Blaszkowska I, Kotarski J (2001) Total antioxidant status of peritoneal fluid in infertile women. Eur J Obstet Gynecol Reprod Biol 94(2):261–263 Dong M, Shi Y, Cheng Q, Hao M (2001) Increased nitric oxide in peritoneal fluid from women with idiopathic infertility and endometriosis. J Reprod Med 46:887–891 Lambrinoudaki IV, Augoulea A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A, Papadias C, Creatsas G (2009) Measurable serum markers of oxidative stress response in women with endometriosis. Fertil Steril 91(1):46–50 Wang Y, Sharma RK, Falcone T, Goldberg J, Agarwal A (1997) Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility. Fertil Steril 68:826–830 Ho HN, Wu MY, Chen SU, Chao KH, Chen CD, Yang YS (1997) Total antioxidant status and nitric oxide do not increase in peritoneal fluids from women with endometriosis. Hum Reprod 12:2810–2815 Ota H, Igarashi S, Hatazawa J, Tanaka T (1999) Endometriosis and free radicals. Gynecol Obstet Invest 48:29–35 Murphy AA, Santanam N, Morales AJ, Parthasarathy S (1998) Lysophosphatidyl choline, a chemotactic factor for monocytes/T-lymphocytes is elevated in endometriosis. J Clin Endocrinol Metabol 83:2110–2113 Ota H, Igarashi S, Hatazawa J, Tanaka T (1999) Immunohistochemical assessment of superoxide dismutase expression in the endometrium in endometriosis and adenomyosis. Fertil Steril 72:129–134 Ota H, Igarashi S, Kato N, Tanaka T (2000) Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril 74:313–318 Jackson L, Schisterman E, Day-Rao R, Browne R, Armstrong D (2005) Oxidative stress and endometriosis. Hum Reprod 20:2014–2020 Portz DM, Elkins TE, White R, Warren J, Adadevoh S, Randolph J (1991) Oxygen free radicals and pelvic adhesion formation: I. Blocking oxygen free radical toxicity to prevent adhesion formation in an endometriosis model. Int J Fertil 36:39–42 ASRM (2004) Endometriosis and infertility. Fertil Steril 82(1):S40–S45 Mahutte NG, Arici A (2002) New advances in the understanding of endometriosis related infertility. J Reprod Immunol 55:73–83 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 Doody MC, Gibbons WE, Buttram VC Jr (1988) Linear regression analysis of ultrasound follicular growth series: evidence for an abnormality of follicular growth in endometriosis patients. Fertil Steril 49:47–51 Grant A (1966) Additional sterility factors in endometriosis. Fertil Steril 17:514–519 Wardle PG, Mitchell JD, McLaughlin EA, Ray BD, McDermott A, Hull MG (1985) Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility. Lancet 2:236–239 Garrido N, Navarro J, Garcia-Velasco J, Remoh J, Pellice A, Simon C (2002) The endometrium versus embryonic quality in endometriosis-related infertility. Hum Reprod Update 8:95–103 Osborn B, Haney AF, Misukonis M, Weinberg JB (2002) Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility. Fertil Steril 77:46–51 Curtis P, Lindsay P, Jackson AE, Shaw RW (1993) Adverse effects on sperm movement characteristic in women with minimal and mild endometriosis. Br J Obstet Gynaecol 100:165–169 Oak MK, Chantler EN, Wiliams CA, Elstein M (1985) Sperm survival studies in peritoneal fluid from infertile women with endometriosis and unexplained infertility. Clin Reprod Fertil 3:297–303 Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, Agarwal A (2009) The impact of peritoneal fluid from healthy women and from women with endometriosis on sperm DNA and its relationship to the sperm deformity index. Fertil Steril 92:61–67 Mansour G, Agarwal A, Radwan E, Sharma R, Goldberg J, Falcone T (2007) DNA damage in metaphase II oocytes is induced by peritoneal fluid from endometriosis patients. ASRM 63rd annual meeting Mansour G, Radwan E, Sharma R, Agarwal A, Falcone T, Goldberg J (2007) DNA damage to embryos incubated in the peritoneal fluid of patients with endometriosis: role in infertility. ASRM 63rd annual meeting Agarwal A, Gupta S, Sikka S (2006) The role of free radicals and antioxidants in reproduction. Curr Opin Obstet Gynecol 18:325–332 Polak G, Rola R, Gogacz M, Koziol-Montewka M, Kotarski J (1999) Malonyldialdehyde and total antioxidant status in the peritoneal fluid of infertile women. Ginecol PII 70:135–140 Toya M, Saito H, Ohta N, Saito T, Kaneko T, Hiroi M (2000) Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer. Fertil Steril 73:344–350 Nakahara K, Saito H, Saito T, Ito M, Ohta N, Sakai N et al (1997) Incidence of apoptotic bodies in membrana granulosa of the patients participating in an in vitro fertilization program. Fertil Steril 67:302–308 Sifer C, Benifla JL, Bringuier AF, Porcher R, Blanc-Layrac G, Madelenat P, Feldman G (2002) Could induced apoptosis of human granulosa cells predict in vitro fertilization-embryo transfer outcome? A preliminary study of 25 women. Eur J Obstet Gynecol Reprod Biol 103:150–153 Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG (1997) Ovarian dysfunction in endometriosis-associated and unexplained infertility. J Assist Reprod Genet 14:554–557 Tummon IS, Maclin VM, Radwanska E, Binor Z, Dmowski WP (1988) Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility. Fertil Steril 50:716–720 Trinder J, Cahill DJ (2002) Endometriosis and infertility: the debate continues. Hum Fertil 5:S21–S27 Mahmood TA, Templeton A (1991) Folliculogenesis and ovulation in infertile women with mild endometriosis. Hum Reprod 6:227–231 Marcoux S, Maheux R, Berube S (1997) Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian collaborative group on endometriosis. N Engl J Med 337:217–222 Parazzini F (1999) Ablation of lesions or no treatment in minimal–mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell’Endometriosi. Hum Reprod 14:1332–1334 Garcia-Velasco JA, Arici A (2004) Surgery for the removal of endometriomas before in vitro fertilization does not increase implantation and pregnancy rates. Fertil Steril 81:1206 Suzuki T, Izumi S, Matsubayashi H, Awaji H, Yoshikata K, Makino T (2005) Impact of ovarian endometrioma on oocytes and pregnancy outcome in in vitro fertilization. Fertil Steril 83:908–913 Parazzini F, Chiaffarino F, Surace M, Chatenoud L, Cipriani S, Chiantera V et al (2004) Selected food intake and risk of endometriosis. Hum Reprod 19:1755–1759 Mier-Cabrera J, Genera-Garcia M, De la Jara-Diaz J, Perichart-Perera O, Vadillo-Ortega F, Hernandez-Guerrero C (2008) Effect of vitamins C and E supplementation on peripherals oxidative stress markers and pregnancy rate in women with endometriosis. Int J Gynecol Obstet 100:252–256 Westphal LM, Polan ML, Trant AS, Mooney SB (2004) A nutritional supplement for improving fertility in women: a pilot study. J Reprod Med 49:289–293 National Academy of Sciences (1989) Recommended dietary allowances. 10th edn. National Academy Press, Washington Ehrenkranz R (1980) Vitamin E and the neonate. Am J Dis Child 134:1157–1168 Palamanda JR, Kehrer JR (1993) Involvement of vitamin E and protein thiols in the inhibition of microsomal lipid peroxidation by glutathione. Lipids 28:427–431 Burton GW, Traber MG (1990) Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr 10:357–382 Hernandez-Guerrero CA, Bujalil-Montenegro L, De la Jara-Diaz J, Mier-Cabrera J, Bouchan-Valencia P (2006) Endometriosis and deficient intake of antioxidant molecules related to peripherals and peritoneal oxidative stress. Ginecol Obstet Mex 74:20–28 Jackson D, Craven RA, Hutson RC, Graze I, Lueth P, Tonge RP, Hartley JL, Nickson JA, Rayner SJ, Johnston C, Dieplinger B, Hubalek M, Wilkinson N, Perren TJ, Kehoe S, Hall GD, Daxenbichler G, Dieplinger H, Selby PJ, Banks RE (2007) Proteomic profiling identifies afamin as a potential biomarker for ovarian cancer. Clin Cancer Res 13:7370–7379 Dieplinger H, Ankerst DP, Burges A, Lenhard M, Lingenhel A, Fineder L, Buchner H, Stieber P (2009) Afamin and apolipoprotein A-IV: novel protein markers for ovarian cancer. Cancer Epidemiol Biomarkers Prev 18:1127–1133 de Muñoz CM, Antonio RJ, Angel LJ, Eduardo M, Adolfo C, Fernando P-G, Sonia H, Alejandra C (1996) Tablas de valor nutritivo de los alimentos. Editorial Pax México, México D.F. Gao X, Martin A, Lin H, Bermudez OI, Tucker KL (2006) α-tocopherol intake and plasma concentrations of hispanic and non-hispanic white elders is associated with dietary intake patters. J Nutr 136:2574–2579 Dennehy CE (2006) The use of herbs and dietary supplements in gynecology: an evidence-based review. J Midwifery Womens Health 51:402–409 Ziaei S, Faghihzadeh S, Sohrabvand F, Lamyian M, Emamgholy T (2001) A randomised placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea. Br J Obstet Gynecol 108:1181–1183 Bruno RS, Leonard SW, Atkinson J, Montine TJ, Ramakrishnan R, Bray TM, Traber MG (2006) Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic Biol Med 40:689–697 Zhang X, Sharma RK, Agarwal A, Falcone T (2005) Effect of pentoxifylline in reducing oxidative stress-induced embryotoxicity. J Assist Reprod Genet 22(11–12):415–417 Lv D, Song H, Clarke J, Shi G (2009) Pentoxifylline versus medical therapies for subfertile women with endometriosis. Cochrane Database Syst Rev 8(3):CD007677 Swarnaker S, Paul S (2009) Curcumin arrests endometriosis by downregulation of matrix metalloproteinase-9 activity. Indian J Biochem Biophys 46(1):59–65 Paul S, Sharma AV, Mahapatra PS, Bhattacharya P, Reiter RJ, Swarnakar S (2008) Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res 44(4):439–449 Guney M, Oral B, Karahan N, Mungan T (2008) Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 89(4):934–942 Xu H, Liu WT, Chu CY, Ng PS, Wang CC, Rogers MS (2009) Antiangiogenic effects of green tea catechin on an experimental endometriosis mouse model. Hum Reprod 24(3):608–618 Defre`re S, Van Langendonckt A, Vaesen S, Jouret M, Gonza′lez Ramos R, Gonzalez D, Donnez J (2006) Iron overload enhances epithelial cell proliferation in endometriotic lesions induced in a murine model. Hum Reprod 21:2810–2816 Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA (1986) Endometriosis in association with uterine anomaly. Am J Obstet Gynecol 154:39–43 Arumugam K, Lim JM (1997) Menstrual characteristics associated with endometriosis. Br J Obstet Gynaecol 104:948–950 Guney M, Nasir S, Oral B, Karahan N, Mungan T (2007) Effect of caffeic acid phenethyl ester on the regression of endometrial explants in an experimental rat model. Reprod Sci 14(3):270–279 Murphy AA, Zhou MH, Malkapuram S, Santanam N, Parthasarathy S, Sidell N (2000) RU486-induced growth inhibition of human endometrial cells. Fertil Steril 71:1014–1019 Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2013 Springer Science+Business Media New York About this chapter Cite this chapter Sekhon, L.H., Agarwal, A. (2013). Endometriosis and Oxidative Stress. In: Agarwal, A., Aziz, N., Rizk, B. (eds) Studies on Women's Health. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-041-0_9 Download citation DOI: https://doi.org/10.1007/978-1-62703-041-0_9 Published: Publisher Name: Humana Press, Totowa, NJ Print ISBN: 978-1-62703-040-3 Online ISBN: 978-1-62703-041-0 eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)