The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary Syndrome

Year 2018, Volume: 35 Issue: 4, 306 - 310, 01.07.2018

Esra Nur Tola Nadiye Köroğlu Merve Ergin Hilmi Baha Oral Abdülkadir Turgut Özcan Erel

Abstract

Background: Oxidative stress has been proposed as a potential trigger in the etiopathogenesis of polycystic ovary syndrome-related infertility. Thiol/disulphide homeostasis, a recently identified oxidative stress marker, is one of the antioxidant mechanism in humans with critical roles in folliculogenesis and ovulation.Aims: To investigate follicular fluid thiol/disulphide homeostasis in the etiopathogenesis of polycystic ovary syndrome and to determine its association with in vitro fertilization outcome. The study procedures were approved by the local ethics committee.Study Design: Cross-sectional study.Methods: Follicular fluid from 22 women with polycystic ovary syndrome and 20 ovulatory controls undergoing in vitro fertilization treatment was sampled. Thiol/disulphide homeostasis was analyzed via a novel spectrophotometric method.Results: Follicular native thiol levels, as well as the native thiol/total thiol ratio, were lower in the polycystic ovary syndrome group than in the non-polycystic ovary syndrome group (p=0.041 and p<0.0001, respectively). Disulphide levels, disulphide/native thiol, and disulphide/total thiol ratios were increased in the polycystic ovary syndrome group (p<0.0001). A positive correlation between the fertilization rate and native thiol (p=0.01, r=0.53) and total thiol (p=0.01, r=0.052) among polycystic ovary syndrome patients was found. A positive predictive effect of native thiol level on the fertilization rate in the polycystic ovary syndrome group was also found (p=0.03, β=0.45, 95% CI= 0.031-0.643).Conclusion: Deterioration of thiol/disulphide homeostasis, especially elevated disulphide levels, could be one of the etiopathogenetic mechanisms in polycystic ovary syndrome. Increased native thiol levels are related to the fertilization rate among polycystic ovary syndrome patients and are positive predictors of the fertilization rate among polycystic ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be important in the treatment of polycystic ovary syndrome to increase in vitro fertilization success.

Keywords

Follicular fluid, in vitro fertilization, polycystic ovary syndrome, thiol/disulphide homeostasis

References

• 1. Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod 2012;27:3067-73.
• 2. Li R, Zhang Q, Yang D, Li S, Lu S, Wu X, et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod 2013;28:2562-9.
• 3. Tola EN, Mungan MT, Uğuz AC, Naziroğlu M. Intracellular Ca2+ and antioxidant values induced positive effect on fertilisation ratio and oocyte quality of granulosa cells in patients undergoing in vitro fertilisation. Reprod Fertil Dev 2013;25:746-52.
• 4. Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med 2015;33:1567-71.
• 5. Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, et al. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril 2004;81:973-6.
• 6. Tatemoto H, Sakurai N, Muto N. Protection of porcine oocytes against apoptotic cell death caused by oxidative stress during In vitro maturation: role of cumulus cells. Biol Reprod 2000;63:805-10.
• 7. Turan V, Sezer ED, Zeybek B, Sendag F. Infertility and the presence of insulin resistance are associated with increased oxidative stress in young, non-obese Turkish women with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 2015;28:119-23.
• 8. Hyderali BN, Mala K. Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol 2015;191:15-22.
• 9. Go YM, Jones DP. Thiol/disulfide redox states in signaling and sensing. Crit Rev Biochem Mol Biol 2013;48:173-81.
• 10. Ziegler DM. Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Annu Rev Biochem 1985;54:305-29.
• 11. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326-32.
• 12. Yildirim M, Turkyilmaz E, Neselioglu S, Alisik M, Avsar AF. Dynamic ThiolDisulphide Status in Polycystic Ovary Syndrome and Its Association with the Pathogenesis of the Disease. Gynecol Obstet Inves 2017;82:54-9.
• 13. Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol 2009;21:219-22.
• 14. Verit FF, Erel O. Oxidative stress in nonobese women with polycystic ovary syndrome: correlations with endocrine and screening parameters. Gynecol Obstet Invest 2008;65:233-9.
• 15. Tsai-Turton M, Luderer U. Opposing effects of glutathione depletion and folliclestimulating hormone on reactive oxygen species and apoptosis in cultured preovulatory rat follicles. Endocrinology 2006;147:1224-36.
• 16. Cataldo NA, Dumesic DA, Goldsmith PC, Jaffe RB. Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic ovary syndrome: relationship to apoptosis. Hum Reprod 2000;15:1889-97.
• 17. Chattopadhayay R, Ganesh A, Samanta J, Jana SK, Chakravarty BN, Chaudhury K. Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecol Obstet Invest 2010;69:197- 202.
• 18. El Mouatassim S, Guerin P, Menezo Y. Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation. Mol Hum Reprod 1999;5:720-5.
• 19. Agarwal A, Gupta S, Sikka S. The role of free radicals and antioxidants in reproduction. Curr Opin Obstet Gynecol 2006;18:325-32.
• 20. Jancar N, Kopitar AN, Ihan A, Virant Klun I, Bokal EV. Effect of apoptosis and reactive oxygen species production in human granulosa cells on oocyte fertilization and blastocyst development. J Assist Reprod Genet 2007;24:91-7.
• 21. Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Human Reprod 2003;18:2270-4.
• 22. Borowiecka M, Wojsiat J, Polac I, Radwan M, Radwan P, Zbikowska HM. Oxidative stress markers in follicular fluid of women undergoing in vitro fertilization and embryo transfer. Syst Biol Reprod Med 2012;58:301-5.