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Journal of Assisted Reproduction and Genetics

, Volume 33, Issue 9, pp 1223–1230 | Cite as

Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage?

  • Pınar ÖzcanEmail author
  • Cem Fıçıcıoğlu
  • Ozge Kizilkale
  • Mert Yesiladali
  • Olgu Enis Tok
  • Ferda Ozkan
  • Mukaddes Esrefoglu
Reproductive Physiology and Disease

Abstract

Purpose

We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage.

Methods

Twenty-four adult female Sprague–Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH-positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed.

Result(s)

The mean serum AMH concentrations were 1.3 ± 0.19, 0.16 ± 0.03, and 0.27 ± 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03).

Conclusion(s)

CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known.

Keywords

AMH Ovarian reserve Oxidative damage 8'OHdG Coenzyme Q10 

Notes

Compliance with ethical standards

The study protocol was approved by the Institutional Animal Care and Use Committee of Yeditepe University. All procedures were performed in accordance with the National Academy of Science’s Guide for Care and Use of Laboratory Animals (1996).

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Wilson DM, Sofinowski TM, McNeill DR. Repair mechanisms for oxidative DNA damage. Front Biosci. 2003;1(8):963–81.Google Scholar
  2. 2.
    Kasai H, Tanooka H, Nishimura S. Formation of 8-hydroxyguanine residues in DNA by X-irradiation. Gan. 1984;75(12):1037–9.PubMedGoogle Scholar
  3. 3.
    Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res. 1997;387(3):147–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Klaunig JE, Wang Z, Pu X, Zhou S. Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol. 2011;254(2):86–99.CrossRefPubMedGoogle Scholar
  5. 5.
    Nickel A, Kohlhaas M, Maack C. Mitochondrial reactive oxygen species production and elimination. J Mol Cell Cardiol. 2014;73:26–33.CrossRefPubMedGoogle Scholar
  6. 6.
    Meldrum DR. Aging gonads, glands, and gametes: immutable or partially reversible changes? Fertil Steril. 2013;99(1):1–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Li Q, Geng X, Zheng W, Tang J, Xu B, Shi Q. Current understanding of ovarian aging. Sci China Life Sci. 2012;55(8):659–69.CrossRefPubMedGoogle Scholar
  8. 8.
    Bentov Y, Casper RF. The aging oocyte—can mitochondrial function be improved? Fertil Steril. 2013;99(1):18–22.CrossRefPubMedGoogle Scholar
  9. 9.
    Santos-Ocana C, Do TQ, Padilla S, Navas P, Clarke CF. Uptake of exogenous coenzyme Q and transport to mitochondria is required for bc1 complex stability in yeast coq mutants. J Biol Chem. 2002;277(13):10973–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Villalba JM, Navas P. Plasma membrane redox system in the control of stress-induced apoptosis. Antioxid Redox Signal. 2000;2000(2):213–30.CrossRefGoogle Scholar
  11. 11.
    Pignatti C, Cocchi M, Weiss H. Coenzyme Q10 levels in rat heart of different age. Biochem Exp Biol. 1980;16(1):39–42.PubMedGoogle Scholar
  12. 12.
    Quinzii CM, Hirano M, DiMauro S. CoQ10 deficiency diseases in adults. Mitochondrion. 2007;(7Suppl):122–6Google Scholar
  13. 13.
    Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, et al. Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Fertil Steril. 2004;81(1):93–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Bentinger M, Tekle M, Brismar K, Chojnacki T, Swiezewska E, Dallner G. Stimulation of coenzyme Q synthesis. Biofactors. 2008;32(1-4):99–111.CrossRefPubMedGoogle Scholar
  15. 15.
    Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, et al. Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. J Int Soc Sports Nutr. 2008;4(5):8.CrossRefGoogle Scholar
  16. 16.
    Mizuno K, Tanaka M, Nozaki S, Mizuma H, Ataka S, Tahara T, et al. Antifatigue effects of coenzyme Q10 during physical fatigue. Nutrition. 2008;24(4):293–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Siddik Z. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22:7265–79.CrossRefPubMedGoogle Scholar
  18. 18.
    Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update. 2012;18(5):525–35.CrossRefPubMedGoogle Scholar
  19. 19.
    Tangir J, Zelterman D, Ma W, Schwartz PE. Reproductive function after conservative surgery and chemotherapy for malignant germ cell tumors of the ovary. Obstet Gynecol. 2003;101(2):251–7.PubMedGoogle Scholar
  20. 20.
    Yuksel A, Bildik G, Senbabaoglu F, Akin N, Arvas M, Unal F, et al. The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells. Hum Reprod. 2015;30(12):2926–35.PubMedGoogle Scholar
  21. 21.
    Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol. 2009;61(3):223–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Yucebilgin MS, Terek MC, Ozsaran A, Akercan F, Zekioglu O, Isik E, et al. Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility. Aust N Z J Obstet Gynaecol. 2004;44(1):6–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Ozcan P, Fıçıcıoğlu C, Yıldırım ÖK, Özkan F, Akkaya H, Aslan İ. Protective effect of resveratrol against oxidative damage to ovarian reserve in female Sprague-Dawley rats. Reprod Biomed Online. 2015;31(3):404–10.CrossRefPubMedGoogle Scholar
  24. 24.
    Li X, Yang S, Lv X, Sun H, Weng J, Liang Y, et al. The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats. J Gynecol Oncol. 2013;24(2):177–85.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dale O, Mortensen B, Thommesen L, Hagen B. Cisplatin toxicity in the rat may be influenced by anaesthetic agents. Acta Anaesthesiol Scand. 2000;44(6):770.CrossRefPubMedGoogle Scholar
  26. 26.
    Kwong LK, Kamzalov S, Rebrin I, Bayne AC, Jana CK, Morris P, et al. Effects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radic Biol Med. 2002;33(5):627–38.CrossRefPubMedGoogle Scholar
  27. 27.
    Tilly JL. Ovarian follicle counts—not as simple as 1, 2, 3. Reprod Biol Endocrinol. 2003;6(1):11.CrossRefGoogle Scholar
  28. 28.
    Yeh J, Kim BS, Peresie J. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. Am J Obstet Gynecol. 2008;198(4):463.e1-6.CrossRefGoogle Scholar
  29. 29.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.CrossRefPubMedGoogle Scholar
  30. 30.
    Bentov Y, Esfandiari N, Burstein E, Casper RF. The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients. Fertil Steril. 2010;93(1):272–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Gendelman M, Roth Z. Incorporation of coenzyme Q10 into bovine oocytes improves mitochondrial features and alleviates the effects of summer thermal stress on developmental competence. Biol Reprod. 2012;87(5):118.CrossRefPubMedGoogle Scholar
  32. 32.
    Quinzii CM, Tadesse S, Naini A, Hirano M. Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts. PLoS ONE. 2012;7(2):30606.CrossRefGoogle Scholar
  33. 33.
    Burstein E, Perumalsamy A, Bentov Y, Esfandiari N, Jurisicova A, Casper RF. Co-enzyme Q10 supplementation improves ovarian response and mitochondrial function in aged mice. Fertil Steril. 2009;92(3-1):31.CrossRefGoogle Scholar
  34. 34.
    Ben-Meir A, Burstein E, Borrego-Alvarez A, Chong J, Wong E, Yavorska T, et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell. 2015;14(5):887–95.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Bentov Y, Hannam T, Jurisicova A, Esfandiari N, Casper RF. Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment. Clin Med Insights Reprod Health. 2014;8:31–6.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    El Refaeey A, Selem A, Badawy A. Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome. Reprod Biomed Online. 2014;29(1):119–24.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Pınar Özcan
    • 1
    • 2
    Email author
  • Cem Fıçıcıoğlu
    • 3
  • Ozge Kizilkale
    • 3
  • Mert Yesiladali
    • 3
  • Olgu Enis Tok
    • 4
  • Ferda Ozkan
    • 5
  • Mukaddes Esrefoglu
    • 4
  1. 1.Department of Obstetrics and GynecologyBezmialem University Faculty of MedicineİstanbulTurkey
  2. 2.Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive BiologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of Obstetrics and Gynecology, Faculty of MedicineYeditepe UniversityIstanbulTurkey
  4. 4.Department of Histology and EmbryologyBezmialem University Faculty of MedicineİstanbulTurkey
  5. 5.Department of Pathology, Faculty of MedicineYeditepe UniversityIstanbulTurkey

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