Skip to main content

Advertisement

SpringerLink
Log in

Increased concentration of 8-hydroxy-2′-deoxyguanosine in follicular fluid of infertile women with endometriosis

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Impaired oocyte quality and oxidative stress might be involved in the pathogenesis of endometriosis-related infertility. To improve our understanding of the role of oxidative stress in this condition, we compare eight oxidative stress markers from each stage, including the simultaneous analysis of lipids, proteins and DNA damage, in the serum and follicular fluid of infertile women with endometriosis and infertile controls undergoing controlled ovarian stimulation for intracytoplasmic sperm injection. In total, 87 serum samples (43 with endometriosis, 44 controls) and 61 follicular fluid samples (29 with endometriosis, 32 controls) free of blood contamination upon visual inspection and presenting granulosa cells alone or granulosa cells plus a retrieved mature oocyte were collected on the day of oocyte retrieval. Total hydroperoxides, malondialdehyde, advanced oxidation protein products, glutathione, superoxide dismutase (SOD) and total antioxidant capacity (TAC) were determined by spectrophotometry, vitamin E by high-performance liquid chromatography and 8-hydroxy-2′–deoxyguanosine (8OHdG) by enzyme-linked immunosorbent assay. The endometriosis group showed higher serum concentrations of glutathione and SOD, lower serum concentrations of TAC and higher follicular concentrations of 8OHdG and vitamin E compared with infertile controls. These data indicate both systemic and follicular oxidative stress in infertile patients with endometriosis. For the first time, we demonstrate the presence of oxidative DNA damage, represented by higher 8OHdG concentrations in the follicular microenvironment of these patients, possibly related to compromised oocyte quality and associated with the pathogenesis of endometriosis-related infertility.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

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

    Article  Google Scholar 

  • Agarwal A, Saleh RA, Bedaiwy MA (2003) Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril 79:829–843

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • Agarwal A, Said TM, Bedaiwy MA, Banerjee J, Alvarez JG (2006) Oxidative stress in an assisted reproductive techniques setting. Fertil Steril 86:503–512

    Article  CAS  PubMed  Google Scholar 

  • Andrade AZ, Rodrigues JK, Dib LA, Romao GS, Ferriani RA, Jordao Junior AA, Navarro PA (2010) Serum markers of oxidative stress in infertile women with endometriosis. Rev Bras Ginecol Obstet 32:279–285

    Article  PubMed  Google Scholar 

  • Arnaud J, Fortis I, Blachier S, Kia D, Favier A (1991) Simultaneous determination of retinol, alpha-tocopherol and beta-carotene in serum by isocratic high-performance liquid chromatography. J Chromatogr 572:103–116

    Article  CAS  PubMed  Google Scholar 

  • Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, Sharma RK (2000) The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med 45:314–320

    CAS  PubMed  Google Scholar 

  • Barcelos ID, Vieira RC, Ferreira EM, Martins WP, Ferriani RA, Navarro PA (2009) Comparative analysis of the spindle and chromosome configurations of in vitro-matured oocytes from patients with endometriosis and from control subjects: a pilot study. Fertil Steril 92:1749–1752

    Article  PubMed  Google Scholar 

  • Bordin L, Fiore C, Dona G, Andrisani A, Ambrosini G, Faggian D, Plebani M, Clari G, Armanini D (2010) Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA-125, and human epididymal secretory protein E4 as combined parameters in endometriosis. Fertil Steril 94:1616–1621

    Article  CAS  PubMed  Google Scholar 

  • Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519

    Article  CAS  PubMed  Google Scholar 

  • Campos Petean C, Ferriani RA, dos Reis RM, de Moura MD, Jordao AA Jr, Navarro PA (2008) Lipid peroxidation and vitamin E in serum and follicular fluid of infertile women with peritoneal endometriosis submitted to controlled ovarian hyperstimulation: a pilot study. Fertil Steril 90:2080–2085

    Article  PubMed  Google Scholar 

  • Choi YS, Cho S, Seo SK, Park JH, Kim SH, Lee BS (2015) Alteration in the intrafollicular thiol-redox system in infertile women with endometriosis. Reproduction 149:155–162

    Article  CAS  PubMed  Google Scholar 

  • Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum, New York

    Google Scholar 

  • Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM (2010) World health organization reference values for human semen characteristics. Hum Reprod Update 16:231–245

    Article  PubMed  Google Scholar 

  • Costa CM, Santos RCC, Lima ES (2006) A simple automated procedure for thiol measurement in human serum samples. J Bras Patol Med Lab 42:5

    Article  Google Scholar 

  • Da Broi MG, Navarro PA (2015) Oxidative stress and oocyte quality: ethiopathogenic mechanisms of minimal/mild endometriosis-related infertility. Cell Tissue Res 364:1-7

    Article  PubMed  Google Scholar 

  • Da Broi MG, Malvezzi H, Paz CC, Ferriani RA, Navarro PA (2014) Follicular fluid from infertile women with mild endometriosis may compromise the meiotic spindles of bovine metaphase II oocytes. Hum Reprod 29:315–323

    Article  PubMed  Google Scholar 

  • Donabela FC, Andrade AZ, Rodrigues JK, Dib LA, Jordão AA, Navarro PA (2010) Serum markers of oxidative stress in infertile women with endometriosis and controls. ASRM 66th Annual Meeting. Fertil Steril 94:S40

    Article  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • El-Shahat KH, Kandil M (2012) Antioxidant capacity of follicular fluid in relation to follicular size and stage of estrous cycle in buffaloes. Theriogenology 77:1513–1518

    Article  CAS  PubMed  Google Scholar 

  • Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37:277–285

    Article  CAS  PubMed  Google Scholar 

  • Evans MD, Dizdaroglu M, Cooke MS (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567:1–61

    Article  CAS  PubMed  Google Scholar 

  • Fujii J, Iuchi Y, Okada F (2005) Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol 3:43

    Article  PubMed  PubMed Central  Google Scholar 

  • Galli F, Piroddi M, Annetti C, Aisa C, Floridi E, Floridi A (2005) Oxidative stress and reactive oxygen species. Contrib Nephrol 149:240–260

    Article  CAS  PubMed  Google Scholar 

  • Giorgi VS, Da Broi MG, Paz CC, Ferriani RA, Navarro PA (2015) N-acetyl-cysteine and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with mild endometriosis. Reprod Sci 23:342–351

    Article  PubMed  Google Scholar 

  • Gupta S, Agarwal A, Krajcir N, Alvarez JG (2006) Role of oxidative stress in endometriosis. Reprod Biomed Online 13:126–134

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A (2008) Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 90:247–257

    Article  CAS  PubMed  Google Scholar 

  • Holoch KJ, Lessey BA (2010) Endometriosis and infertility. Clin Obstet Gynecol 53:429–438

    Article  PubMed  Google Scholar 

  • Hu ML (1994) Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol 233:380–385

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Jana SK, Dutta M, Joshi M, Srivastava S, Chakravarty B, Chaudhury K (2013) 1H NMR based targeted metabolite profiling for understanding the complex relationship connecting oxidative stress with endometriosis. Biomed Res Int 2013:329058

    Article  PubMed  PubMed Central  Google Scholar 

  • Julious SA (2005) Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat 4:287–291

    Article  Google Scholar 

  • Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, Hummelshoj L, Prentice A, Saridogan E, ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group (2005) ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 20:2698–2704

    Article  PubMed  Google Scholar 

  • 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 91:46–50

    Article  CAS  PubMed  Google Scholar 

  • Lancaster GA, Dodd S, Williamson PR (2004) Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract 10:307–312

    Article  PubMed  Google Scholar 

  • Levay PF, Huyser C, Fourie FL, Rossouw DJ (1997) The detection of blood contamination in human follicular fluid. J Assist Reprod Genet 14:212–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Trimarchi JR, Navarro P, Blasco MA, Keefe DL (2003) Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis. J Biol Chem 278:31998–32004

    Article  CAS  PubMed  Google Scholar 

  • Liu F, He L, Liu Y, Shi Y, Du H (2013) The expression and role of oxidative stress markers in the serum and follicular fluid of patients with endometriosis. Clin Exp Obstet Gynecol 40:372–376

    CAS  PubMed  Google Scholar 

  • Meister A (1983) Transport and metabolism of glutathione and gamma-glutamyl amino acids. Biochem Soc Trans 11:793–794

    Article  CAS  PubMed  Google Scholar 

  • 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 peripheral oxidative stress markers and pregnancy rate in women with endometriosis. Int J Gynaecol Obstet 100:252–256

    Article  CAS  PubMed  Google Scholar 

  • Murphy AA, Santanam N, Parthasarathy S (1998) Endometriosis: a disease of oxidative stress? Semin Reprod Endocrinol 16:263–273

    Article  CAS  PubMed  Google Scholar 

  • Navarro PA, Liu L, Keefe DL (2004) In vivo effects of arsenite on meiosis, preimplantation development, and apoptosis in the mouse. Biol Reprod 70:980–985

    Article  CAS  PubMed  Google Scholar 

  • Navarro PA, Liu L, Ferriani RA, Keefe DL (2006) Arsenite induces aberrations in meiosis that can be prevented by coadministration of N-acetylcysteine in mice. Fertil Steril 85 (Suppl 1):1187–1194

    Article  CAS  PubMed  Google Scholar 

  • Nwose EU, Jelinek HF, Richards RS, Kerr PG (2008) The “vitamin E regeneration system” (VERS) and an algorithm to justify antioxidant supplementation in diabetes—a hypothesis. Med Hypotheses 70:1002–1008

    Article  CAS  PubMed  Google Scholar 

  • Prieto L, Quesada JF, Cambero O, Pacheco A, Pellicer A, Codoceo R, Garcia-Velasco JA (2012) Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis. Fertil Steril 98:126–130

    Article  CAS  PubMed  Google Scholar 

  • Ruder EH, Hartman TJ, Blumberg J, Goldman MB (2008) Oxidative stress and antioxidants: exposure and impact on female fertility. Hum Reprod Update 14:345–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seino T, Saito H, Kaneko T, Takahashi T, Kawachiya S, Kurachi H (2002) Eight-hydroxy-2′-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program. Fertil Steril 77:1184–1190

    Article  PubMed  Google Scholar 

  • Sim J, Lewis M (2012) The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol 65:301–308

    Article  PubMed  Google Scholar 

  • Singh AK, Chattopadhyay R, Chakravarty B, Chaudhury K (2013) Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol 42:116–124

    Article  CAS  PubMed  Google Scholar 

  • Szczepanska M, Kozlik J, Skrzypczak J, Mikolajczyk M (2003) Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril 79:1288–1293

    Article  PubMed  Google Scholar 

  • Tamura H, Takasaki A, Miwa I, Taniguchi K, Maekawa R, Asada H, Taketani T, Matsuoka A, Yamagata Y, Shimamura K, Morioka H, Ishikawa H, Reiter RJ, Sugino N (2008) Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res 44:280–287

    Article  CAS  PubMed  Google Scholar 

  • Tatemoto H, Muto N, Sunagawa I, Shinjo A, Nakada T (2004) Protection of porcine oocytes against cell damage caused by oxidative stress during in vitro maturation: role of superoxide dismutase activity in porcine follicular fluid. Biol Reprod 71:1150–1157

    Article  CAS  PubMed  Google Scholar 

  • Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the staff of the Human Reproduction Division, Department of Obstetrics and Gynecology, Ribeirao Preto School of Medicine, University of Sao Paulo (FMRP-USP), especially Maria Cristina Picinato and Roberta Cristina Giorgenon for FF collection, to the Nutrition and Metabolism Laboratory, FMRP-USP, especially Paula Payão and Virginia Lipoli for technical support to Jhenifer Kliemchen Rodrigues for assisting with the quantification of OS markers and to Suleimy Cristina Mazin for the statistical advice.

Author information

Authors and Affiliations

  1. Human Reproduction Division, Department of Obstetrics and Gynecology, Ribeirão Preto School of Medicine, University of São Paulo, Avenida Bandeirantes, 3900 Monte Alegre, Ribeirao Preto, SP, Brazil, CEP: 14049-900

    Michele G. Da Broi, Felipe O. de Albuquerque, Aline Z. de Andrade, Rafaela L. Cardoso & Paula A. Navarro

  2. Nutrition and Metabolism Laboratory, Department of Internal Medicine, Ribeirão Preto School of Medicine, University of Sao Paulo, Ribeirão Preto, SP, Brazil

    Alceu A. Jordão Junior

Authors
  1. Michele G. Da Broi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Felipe O. de Albuquerque
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aline Z. de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafaela L. Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alceu A. Jordão Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paula A. Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele G. Da Broi.

Additional information

This study received financial support from the National Council for Scientific and Technological Development (CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico; 474858/2009-0; 309056/2009-8; 503867/2010-1) and the Sao Paulo Research Foundation (FAPESP – Fundação de Amparo à Pesquisa do Estado de São Paulo; 2008/58197-6; 2008/56373-1; 2014/15866-6).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Da Broi, M.G., de Albuquerque, F.O., de Andrade, A.Z. et al. Increased concentration of 8-hydroxy-2′-deoxyguanosine in follicular fluid of infertile women with endometriosis. Cell Tissue Res 366, 231–242 (2016). https://doi.org/10.1007/s00441-016-2428-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-016-2428-4

Keywords

Search

Navigation