Antioxidant effect of genistein on ovarian tissue morphology, oxidant and antioxidant activity in rats with induced polycystic ovary syndrome

Abstract

Background: Oxidative stress is the most frequent cause of female infertility disorders including polycystic ovary syndrome (PCOS). Genistein as a major component of soybean isoflavone scavenges free radicals by antioxidant activities.


Objective: The present study examines the antioxidant effects of genistein on ovarian tissue following experimental PCOS in rats.


Materials and Methods: Twenty female Wistar rat were randomly divided into the following groups (n=5 each group): (I) control group (no treatment); (II) induced PCOS (injection of estradiol valerate); (III) genistein-treated non-PCOS (received genistein); and (IV) genistein-treated PCOS groups. The weight of rats were measured and the blood samples collected and centrifuged. The oxidant and antioxidant activity of plasma and ovaries were measured. All rats were sacrificed under anesthesia, and ovaries were collected and weighted. Histological examination and follicular quality
were assessed by staining.


Results: In histological observation, the induced PCOS rats displayed more number of atretic follicles and the follicular quality in genistein-treated rats was similar to the control groups. The plasma and ovaries malondialdehyde levels significantly increased in PCOS rats (p < 0.001), while the total antioxidant capacity levels, glutathione peroxidase, and superoxide dismutase activities significantly decreased (p < 0.001). The plasma and ovary  malondialdehyde levels significantly decreased in PCOS rats that were treated with genistein (p < 0.001) and the total antioxidant capacity (p < 0.05), glutathione peroxidase, and superoxide dismutase activities significantly increased (p < 0.001).


Conclusion: Treatment with genistein preserved follicular quality by increasing antioxidant activities and scavenging oxidant levels in PCOS rats.


Key words: Genistein, Antioxidant, Ovary, Polycystic, Follicle, Rats.

References
[1] Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol 2004;60: 1–17.

[2] Park HR, Choi Y, Lee HJ, Oh JY, Hong YS, Sung YA. The metabolic syndrome in young Korean women with
polycystic ovary syndrome. Diabetes Res Clin Pract 2007;77: S243–S246.

[3] Carmina E. Genetic and environmental aspect of polycystic ovary syndrome. J Endocrinol Invest 2003; 26: 1151–1159.

[4] Rezvanfar MA, Rezvanfar MA, Ahmadi A, Saadi HA, Baeeri M, Abdollahi M. Mechanistic links between oxidative/nitrosative stress and tumor necrosis factor alpha in letrozole-induced murine polycystic ovary: biochemical and pathological evidences for beneficial effect of pioglitazone. Hum Exp Toxicol 2012; 31: 887–897.

[5] 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.

[6] Showell MG, Brown J, Clarke J, Hart RJ. Antioxidants for female subfertility. Cochrane Database Syst Rev 2013; 8:CD007807.

[7] Zhang D, Luo W, Liao H, Wang C, Sun Y. The effects of oxidative stress to PCOS. Sichuan Da Xue Xue Bao Yi Xue Ban 2008; 39: 421–423.

[8] Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod update 2013; 19:268–288.

[9] Lee JY, Kim HS, Song YS. Genistein as a potential anticancer agent against ovarian. Cancer J Tradit Complement Med 2012; 2: 96–104.

[10] Xu J, Zhu J, Shi C, Guo K, Yew DT. Effects of genistein on hippocampal neurodegeneration of ovariectomized rats. J Mol Neurosci 2007; 31: 101–112.

[11] Yoon K, Kwack SJ, Kim HS, Lee BM. Estrogenic endocrinedisrupting chemicals: molecular mechanisms of actions on putative human diseases. J Toxicol Environ Health B Crit Rev 2014; 7: 127–174.

[12] Romualdi D, Costantini B, Campaqna G, Lanzone A, Guido M. Is there a role for soy isoflavones in the therapeutic approach to polycystic ovary syndrome? Results from a pilot study. Fertil Steril 2008; 90: 1826–1833.

[13] Zhao L, Wang Y, Liu J Wang K, Guo X, Ji B, et al. Protective effects of genistein and puerarin against chronic
alcohol-induced liver injury in mice via antioxidant, antiinflammatory, and anti-apoptotic mechanisms. J Agric
Food Chem 2016; 64: 7291–7297.
[14] Zhang L, Gao M, Zhang T, Chong T, Wang Z, Zhai X. et al. Protective effects of genistein against mono-(2-ethylhexyl) phthalate-induced oxidative damage in prepubertal sertoli cells. Biomed Res Int 2017; 2017: 2032697.

[15] Mitchell JH. Phytoestrogens: involvement in breast and prostate cancer. Handbook of Nutraceuticals and Functional Foods. (Wildsmith, R., ed.): 2001. 99–113.

[16] Nasrabadi HT, Gavami M, Akbarzadeh A, Beheshti R, Mohammadnejad D, Abedelahi A. Preservation of mouse ovarian tissue follicle morphology and ultra-structure after vitrifying in biotechnological protocols. J Ovarian Res 2015; 8: 7.

[17] Walters KA, Allan CM, Handelsman DJ. Rodent models for human polycystic ovary syndrome. Biol Reprod 2012; 86:149, 1–12.

[18] March WA, Moore VM, Willson KJ, Phillips DIW, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010; 25: 544–551.

[19] Choi HD, Kim JH, Chang MJ, Kyu-Youn Y, Shin WG. Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 2011; 25: 1813–1818.

[20] Isobe N, Kitabayashi M, Yoshimura Y. Microvascular distribution and vascular endothelial growth factor expression in bovine cystic follicles. Domest Anim Endocrinol 2005; 29: 634–645.

[21] Medigović IM, Živanović JB, Ajdžanović VZ, Nikolić-Kokić AL, Stanković SD, Trifunović SL, et al. Effects of soy
phytoestrogens on pituitary-ovarian function in middleaged female rats. Endocrine 2015; 50: 764–776.

[22] Pandey V, Singh A, Singh A, Krishna A, Pandey U, Tripathi YB. Role of oxidative stress and low grade inflammation in letrozole-induced polycystic ovary syndrome in the rat. Reprod Biol 2016; 16: 70–77.

[23] Agarwal A, Gupta S, Sekhon L, Shah R. Redox considerations in female reproductive function and assisted
reproduction: from molecular mechanisms to health implications. Antioxid Redox Sign 2008; 10: 1375–1403.

[24] Murri M, Luque-Ramirez M, Insenser M, Ojeda-Ojeda M, Escobar- Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 2013; 19:268–288.

[25] Hamilton MG, Dorandeu FM, McCaffery M, Lundy PM, Sawyer TW. Modification of cytosolic free calcium concentrations in human keratinocytes after sulfur mustard exposure. Toxicol In Vitro 1998; 12: 365–372.

[26] Dinger Y, Akcay T, Erdem T, Ilker Saygili E, Gundogdu S. DNA damage, DNA susceptibility to oxidation and glutathione level in women with polycystic ovary syndrome. Scand J Clin Lab Invest 2005; 65: 721–728.

[27] Yeon Lee J, Baw CK, Gupta S, Aziz N, Agarwal A. Role of oxidative stress in polycystic ovary syndrome. Curr
Womens Health Rev 2010; 6: 96–107.

[28] Rimbach G, De Pascual-Teresa S, Ewins BA, Matsugo S, Uchida Y, Minihane AM, et al. Antioxidant and free radical scavenging activity of isoflavone metabolites. Xenobiotica 2003; 33: 913–925.

[29] Zhuang XL, Fu YC, Xu JJ, Kong XX, Chen ZG, Luo LL. Effects of genistein on ovarian follicular development and
ovarian life span in rats. Fitoterapia 2010; 81: 998–1002.

[30] Hernandez-Montes E, Pollard SE, Vauzour D, JofreMontseny L, Rota C, Rimbach G, et al. Activation of
glutathione peroxidase via Nrf1 mediates genistein’s protection against oxidative endothelial cell injury. Biochem Biophys Res Commun 2006; 346: 851–859.

[31] Davis JN, Kucuk O, Djuric Z, Sarkar FH. Soy isoflavone supplementation in healthy men prevents NF-κB activation by TNF in blood lymphocytes. Free Radic Biol Med 2001; 30: 1293–1302.

[32] Mirahmadi SM, Shahmohammadi A, Rousta AM, Azadi MR, Fahanik-Babaei J, Baluchnejadmojarad T, et al.
Soy isoflavone genistein attenuates lipopolysaccharideinduced cognitive impairments in the rat via exerting antioxidative and anti-inflammatory effects. Cytokine 2018;104: 151–159.

[33] Tena G, Moran C, Romero R, Moran S. Ovarian morphology and endocrine function in polycystic ovary syndrome. Arch Gynecol Obstet 2011; 284: 1443–1448.

[34] Weber K, Setchell KD, Stocco DM, Lephart ED. Dietary soyphytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. J Endocrinol 2001; 170: 591–599.

[35] Kafali H, Iriadam M, Ozardali I, Demir N. Letrozole-induced polycystic ovaries in the rat: a new model for cystic ovarian disease. Arch Med Res 2004; 35: 103–108.

[36] Albulescu M, Popovici M. Isoflavones-biochemistry, pharmacology and therapeutic use. Rev Roum Chim 2007; 52:537–550.