The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary

Document Type: Original Article

Authors

1 School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Emergency Sections, Vali-Asr Hospital, Shahrekord University of Medical Sciences, Borujen, Iran

4 Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

5 Department of Urology, St Elizabeth Medical Center, Tufts University, Brighton, MA, USA

6 American Center for Reproductive Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA

Abstract

Objective(s): Several researchers have reported the relationship between infertility in male and varicocele for so many years but the implication of varicocele in female patients is remains elusive. Here, we aim to examine the effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality of rat ovary after the experimental creation of varicocele in female rats.
Materials and Methods: In this study, thirty adult female albino rats were divided into three equal groups: Group 1 as the control group has 10 rats, Group 2 as the sham group has 10 rats and they underwent a sham operation and finally Group 3 has the varicocele group has 10 rats.  Antioxidant assays for superoxide dismutase, glutathioneperoxidase and catalase were performed using specific assay kits and gene expression for Bax, Bmp-15, Hsp-27 and Gdf-9 was done via real time PCR.
Results: The adverse effects of the experimentally induced varicocele were reported and recorded on the left ovary compared to the right sided ovary (no varicocele induction) in the varicocele group. Real time PCR data shows that the expression of Gdf-9, Hsp-27 and Bmp-15 genes were all significantly reduced at P≤0.05.
Conclusion: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/ antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female.

Keywords


1. Yu S, Yap C. Investigating the infertile couple. Ann Acad Med Singapore 2003; 32:611-614.

2. Lim CS, Kiriakidis S, Paleolog EM, Davies AH. The effects of doxycycline and micronized purified flavonoid fraction on human vein wall remodeling are not hypoxia-inducible factor pathway-dependent. J Vasc Surg 2012; 56:1069-1077.

3. Fan CM. Venous Pathophysiology. Semin Intervent Radiol 2005; 22:157-161.

4. Lim CS, Qiao X, Reslan OM, Xia Y, Raffetto JD, Paleolog E, et al. Prolonged mechanical stretch is associated with upregulation of hypoxia-inducible factors and reduced contraction in rat inferior vena cava. J Vasc Surg 2011; 53:764-273.

5. Tinelli A, Prudenzano R, Torsello M, Malvasi A, De Nunzio G, De Mitri I, et al. Suprapubic percutaneous sclero-embolization of symptomatic female pelvic varicocele under local anesthesia. Eur Rev Med Pharmacol Sci 2012; 16:111-117.

6. Dubin L, Amelar R. Varicocele. Urol Clin North Am 1978; 5:563-572.

7. Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, et al. The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med 1999; 45:314-320.

8. Sugino N, Takiguchi S, Kashida S, Karube A, Nakamura Y, Kato H. Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy. Mol Hum Reprod 2000; 6:19-25.

9. Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Curr Womens Health Rev 2010; 6:84-95.

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

11. Du B, Takahashi K, Ishida GM, Nakahara K, Saito H, Kurachi H. Usefulness of intraovarian artery pulsatility and resistance indices measurement on the day of follicle aspiration for the assessment of oocyte quality. Fertil Steril 2006; 85:366-370.

12. Mehlen P, Schulze-Osthoff K, Arrigo A-P. Small stress proteins as novel regulators of apoptosis heat shock protein 27 blocks Fas/APO-1-and staurosporine-induced cell death. J Biol Chem 1996; 271:16510-16514.

13. Préville X, Salvemini F, Giraud S, Chaufour S, Paul C, Stepien G, et al. Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. Exp Cell Res 1999; 247:61-78.

14. Van Voorhis BJ, Dunn MS, Snyder GD, Weiner CP. Nitric oxide: an autocrine regulator of human granulosa-luteal cell steroidogenesis. Endocrinology 1994; 135:1799-1806.

15. Anteby EY, Hurwitz A, Korach O, Revel A, Simon A, Finci-Yeheskel Z, et al. Ovary and ovulation: human follicular nitric oxide pathway: relationship to follicular size, oestradiol concentrations and ovarian blood flow. Hum Reprod 1996; 11:1947-1951.

16. Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J, et al. Cross-talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis: a possible regulatory mechanism for ovarian follicle atresia. Endocrinology 2005; 146:808-815.

17. Erickson GF, Shimasaki S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol 2003; 1:1-20.

18. Hussein TS, Froiland DA, Amato F, Thompson JG, Gilchrist RB. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci 2005; 118:5257-5268.

19. Hussein TS, Thompson JG, Gilchrist RB. Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol 2006; 296:514-521.

20. Hubscher C, Brooks D, Johnson J. A quantitative method for assessing stages of the rat estrous cycle. Biotech Histochem 2005; 80:79-87.

21. Durak I, Yurtarslanl Z, Canbolat O, Akyol Ö. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 1993; 214:103-104.

22. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70:158-169.

23. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121-126.

24. Griess P. Comments on the essay of HH Weselsky and Benedict ‘About some azo compounds’. Chem Ber 1879; 12:426-428.

25. Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology 1996; 48:835-8350.

26. Hendin BN, Kolettis PN, Sharma RK, Thomas AJ Jr, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol 1999; 161:1831-1834.

27. Richet A. Traité pratique d'anatomie médico-chirurgicale: F. Chamerot, Libraire-Éditeur; Published by Lauwereyns, Paris 1877.

28. Galkin E, Grakova L, Naumova E. [Roentgeno-endovascular surgery of hypofunctional ovaries in varicosities of the ovarian veins]. Vestn Rentgenol Radiol 1990; 51-59.

29. Ikeda M, Kodama H, Fukuda J, Shimizu Y, Murata M, Kumagai J, et al. Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod 1999; 61:393-399.

30. Onur R, Semerciöz A, Orhan I, Yekeler H. The effects of melatonin and the antioxidant defence system on apoptosis regulator proteins (Bax and Bcl-2) in experimentally induced varicocele. Urol Res 2004; 32:204-208.

31. Arrigo AP. Hsp27: novel regulator of intracellular redox state. IUBMB life 2001; 52:303-307.

32. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 2000; 279:L1005-L1028.

33. Dimmeler S, Haendeler J, Sause A, Zeiher AM. Nitric oxide inhibits APO-1/Fas-mediated cell death. Cell Growth Differ 1998; 9:415-422.

34. Abbasi M, Akbari M, Amidi F, Kashani IR, Mahmoudi R, Sobhani A, et al. Nitric oxide acts through different signaling pathways in maturation of cumulus cell-enclosed mouse oocytes. DARU J Pharm Sci 2009; 17:48-52.

35. Morita Y, Perez GI, Paris F, Miranda SR, Ehleiter D, Haimovitz-Friedman A, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 2000; 6:1109-1114.

36. De Felici M, Di Carlo A, Pesce M, Iona S, Farrace M, Piacentini M. Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo. Cell Death Differ 1999; 6:908-915.

37. Gebauer G, Peter AT, Onesime D, Dhanasekaran N. Apoptosis of ovarian granulosa cells: Correlation with the reduced activity of ERK‐signaling module. J Cell Biochem 1999; 75:547-554.

38. Zwain I, Zwain IH, Amato P. cAMP-induced apoptosis in granulosa cells is associated with up-regulation of P53 and bax and down-regulation of clusterin. Endocrine Res 2001; 27:233-249.

39. Vitale AM, Gonzalez OM, Parborell F, Irusta G, Campo S, Tesone M. Inhibin a increases apoptosis in early ovarian antral follicles of diethylstilbestrol-treated rats. Biol Reprod 2002; 67:1989-1995.

40. Yoon SJ, Choi KH, Lee KA. Nitric oxide‐mediated inhibition of follicular apoptosis is associated with HSP70 Induction and Bax suppression. Mol Reprod Dev 2002; 61:504-510.

41. Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 2008; 14:159-177.

42. Gode F, Gulekli B, Dogan E, Korhan P, Dogan S, Bige O, et al. Influence of follicular fluid GDF9 and BMP15 on embryo quality. Fertil Steril 2011; 95:2274-2278.

43. Hiromura T, Nishioka T, Nishioka S, Ikeda H, Tomita K. Reflux in the left ovarian vein: analysis of MDCT findings in asymptomatic women. Am J Roentgenol 2004; 183:1411-1415.