Normotensive rats with PCOS exhibit the hypertensive pattern: focus on oxidative stress

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  • 1 Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  • | 2 Department of Gynecology and Obstetrics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  • | 3 University Clinic for Gynecology and Obstetrics ‘Narodni Front’, Belgrade, Serbia
  • | 4 Department of Cytology, Institute for Biological Research ‘Siniša Stanković’ – National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
  • | 5 Department of Dermatovenerology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  • | 6 Clinic for Rehabilitation ‘Dr Miroslav Zotović’, Belgrade, Serbia
  • | 7 Department for Medical Statistics and Informatics, School of Dental Medicine, University of Belgrade, Belgrade, Serbia
  • | 8 Department of Human Pathology, I.M. Sechenoov First Moscow State Medical University, Moscow, Russia

Correspondence should be addressed to J Joksimovic Jovic; Email: jovana_joksimovic@yahoo.com
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Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. In this study, we aimed to investigate the potential strain differences in ovarian morphology, hemodynamic, and biochemical characteristics in an androgen-induced PCOS rat model. A total of 24 rats of 3 weeks old (12 Wistar Kyoto – WK and 12 spontaneously hypertensive rats – SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily s.c. injections of testosterone enanthate (1 mg/100 g body weight) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic, and cystic follicles). Ultrasonographically, a significant decrease in ovarian volume (OV) was registered in PCOS groups but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial, and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, thiobarbituric acid reactive substance and superoxide anion radical levels were higher in both strains, while superoxide dismutase and glutathione were significantly lowered.

Supplementary Materials

    • Supplementary Table. Parameters evaluated from the study

 

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  • Aguilar E, Rodriguez Padilla ML, Bellido C, Tena-Sempere M & Pinilla L 1992 Changes in follicle-stimulating hormone secretion in spontaneously hypertensive rats. Neuroendocrinology 56 8593. (https://doi.org/10.1159/000126212)

    • Search Google Scholar
    • Export Citation
  • Aladashvili-Chikvaidze N, Kristesashvili J & Gegechkori M 2015 Types of reproductive disorders in underweight and overweight young females and correlations of respective hormonal changes with BMI. Iranian Journal of Reproductive Medicine 13 135140.

    • Search Google Scholar
    • Export Citation
  • Alves ED, Bonfá ALO, Pigatto GR, Anselmo-Franci JA, Achcar JA, Parizotto NA & Montrezor LH 2019 Photobiomodulation can improve ovarian activity in polycystic ovary syndrome-induced rats. Journal of Photochemistry and Photobiology: B, Biology 194 613. (https://doi.org/10.1016/j.jphotobiol.2019.03.006)

    • Search Google Scholar
    • Export Citation
  • Amiri M, Ramezani Tehrani F, Behboudi-Gandevani S, Bidhendi-Yarandi R & Carmina E 2020 Risk of hypertension in women with polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Reproductive Biology and Endocrinology 18 23. (https://doi.org/10.1186/s12958-020-00576-1)

    • Search Google Scholar
    • Export Citation
  • Auclair C & Voisin E 1985 Nitroblue tetrazolium reduction. In Handbook of Methods for Oxygen Radical Research, pp. 123132. Ed Greenwald A Boca Raton: CRC Press Press.

    • Search Google Scholar
    • Export Citation
  • Bas D, Abramovich D, Hernandez F & Tesone M 2011 Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Cell Biology International 35 423429. (https://doi.org/10.1042/CBI20100542)

    • Search Google Scholar
    • Export Citation
  • Beutler E 1982 Catalase. In Red Cell Metabolism, A Manual of Biochemical Methods, 3 rd ed., pp. 105106. New York: Grune and Stratton.

  • Beutler E 1984 Superoxide dismutase. In Red Cell Metabolism, A Manual of Biochemical Methods, 2 nd ed., pp. 8385. Ed Beutler E New York: Grune & Stratton.

    • Search Google Scholar
    • Export Citation
  • Chen MJ, Yang WS, Yang JH, Chen CL, Ho HN & Yang YS 2007 Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome. Hypertension 49 14421447. (https://doi.org/10.1161/HYPERTENSIONAHA.106.083972)

    • Search Google Scholar
    • Export Citation
  • Chen X, Huang L, Tan HY, Li H, Wan Y, Cowley M, Veldhuis JD & Chen C 2017 Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice. Reproduction 153 267276. (https://doi.org/10.1530/REP-16-0341)

    • Search Google Scholar
    • Export Citation
  • Crofton JT, Ota M & Share L 1993 Role of vasopressin, the renin-angiotensin system and sex in Dahl salt-sensitive hypertension. Journal of Hypertension 11 10311038. (https://doi.org/10.1097/00004872-199310000-00005)

    • Search Google Scholar
    • Export Citation
  • Dadachanji R, Shaikh N & Mukherjee S 2018 Genetic variants associated with yperandrogenemia in PCOS pathophysiology. Genetics Research International 2018 7624932. (https://doi.org/10.1155/2018/7624932)

    • Search Google Scholar
    • Export Citation
  • Dickhout JG & Lee RM 1998 Blood pressure and heart rate development in young spontaneously hypertensive rats. American Journal of Physiology 274 H794H800. (https://doi.org/10.1152/ajpheart.1998.274.3.H794)

    • Search Google Scholar
    • Export Citation
  • Elting MW, Korsen TJ, Bezemer PD & Schoemaker J 2001 Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Human Reproduction 16 556560. (https://doi.org/10.1093/humrep/16.3.556)

    • Search Google Scholar
    • Export Citation
  • Feng M, Whitesall S, Zhang Y, Beibel M, D’Alecy L & DiPetrillo K 2008 Validation of volume-pressure recording tail-cuff blood pressure measurements. American Journal of Hypertension 21 12881291. (https://doi.org/10.1038/ajh.2008.301)

    • Search Google Scholar
    • Export Citation
  • Furedi N, Miko A, Aubrecht B, Gaszner B, Feller D, Rostas I, Tenk J, Soos S, Balasko M & Balogh A et al.2016 Regulatory alterations of energy homeostasis in spontaneously hypertensive rats (SHR). Journal of Molecular Neuroscience 59 521530. (https://doi.org/10.1007/s12031-016-0771-2)

    • Search Google Scholar
    • Export Citation
  • Ghowsi M, Khazali H & Sisakhtnezhad S 2018 Evaluation of TNF-α and IL-6 mRNAs expressions in visceral and subcutaneous adipose tissues of polycystic ovarian rats and effects of resveratrol. Iranian Journal of Basic Medical Sciences 21 165174. (https://doi.org/10.22038/IJBMS.2017.24801.6167)

    • Search Google Scholar
    • Export Citation
  • Glintborg D, Hass Rubin K, Nybo M, Abrahamsen B & Andersen M 2015 Morbidity and medicine prescriptions in a nationwide Danish population of patients diagnosed with polycystic ovary syndrome. European Journal of Endocrinology 172 627638. (https://doi.org/10.1530/EJE-14-1108)

    • Search Google Scholar
    • Export Citation
  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS & Tannenbaum SR 1982 Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry 126 131138. (https://doi.org/10.1016/0003-2697(8290118-X)

    • Search Google Scholar
    • Export Citation
  • Holte J, Gennarelli G, Berne C, Bergh T & Lithell H 1996 Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: a sign of a pre-hypertensive state? Human Reproduction 11 2328. (https://doi.org/10.1093/oxfordjournals.humrep.a019028)

    • Search Google Scholar
    • Export Citation
  • IJzerman RG, Stehouwer CD, de Geus EJ, van Weissenbruch MM, Delemarre-van de Waal HA & Boomsma DI 2003 Low birth weight is associated with increased sympathetic activity: dependence on genetic factors. Circulation 108 566571. (https://doi.org/10.1161/01.CIR.0000081778.35370.1B)

    • Search Google Scholar
    • Export Citation
  • Iwasa T, Matsuzaki T, Yano K, Yanagihara R, Tungalagsuvd A, Munkhzaya M, Mayila Y, Kuwahara A & Irahara M 2017 The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats. Hormones and Behavior 93 5361. (https://doi.org/10.1016/j.yhbeh.2017.05.008)

    • Search Google Scholar
    • Export Citation
  • Johansson J, Feng Y, Shao R, Lönn M, Billig H & Stener-Victorin E 2010 Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome. American Journal of Physiology: Endocrinology and Metabolism 299 E551E559. (https://doi.org/10.1152/ajpendo.00323.2010)

    • Search Google Scholar
    • Export Citation
  • Joksimovic J, Selakovic D, Jovicic N, Mitrovic S, Mihailovic V, Katanic J, Milovanovic D & Rosic G 2019 Exercise attenuates anabolic steroids-induced anxiety via hippocampal NPY and MC4 receptor in rats. Frontiers in Neuroscience 13 172. (https://doi.org/10.3389/fnins.2019.00172)

    • Search Google Scholar
    • Export Citation
  • Joksimovic Jovic J, Sretenovic J, Jovic N, Rudic J, Zivkovic V, Srejovic I, Mihajlovic K, Draginic N, Andjic M & Milinkovic M et al.2021 Cardiovascular properties of the androgen-induced PCOS model in rats: the role of oxidative stress. Oxidative Medicine and Cellular Longevity 2021 8862878. (https://doi.org/10.1155/2021/8862878)

    • Search Google Scholar
    • Export Citation
  • Kalhori Z, Azadbakht M, Soleimani Mehranjani M & Shariatzadeh MA 2018 Improvement of the folliculogenesis by transplantation of bone marrow mesenchymal stromal cells in mice with induced polycystic ovary syndrome. Cytotherapy 20 14451458. (https://doi.org/10.1016/j.jcyt.2018.09.005)

    • Search Google Scholar
    • Export Citation
  • Lansdown A & Rees DA 2012 The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target? Clinical Endocrinology 77 791801. (https://doi.org/10.1111/cen.12003)

    • Search Google Scholar
    • Export Citation
  • Liu G, Shi F, Blas-Machado U, Duong Q, Davis VL, Foster WG & Hughes CL 2005 Ovarian effects of a high lactose diet in the female rat. Reproduction, Nutrition, Development 45 185192. (https://doi.org/10.1051/rnd:2005010)

    • Search Google Scholar
    • Export Citation
  • Marchesan LB & Spritzer PM 2019 ACC/AHA 2017 definition of high blood pressure: implications for women with polycystic ovary syndrome. Fertility and Sterility 111 579 .e1587.e1. (https://doi.org/10.1016/j.fertnstert.2018.11.034)

    • Search Google Scholar
    • Export Citation
  • Marcondes FK, Bianchi FJ & Tanno AP 2002 Determination of the estrous cycle phases of rats: some helpful considerations. Brazilian Journal of Biology 62 609614. (https://doi.org/10.1590/s1519-69842002000400008)

    • Search Google Scholar
    • Export Citation
  • Martínez LA, Cifuentes F & Morales MA 2019 Ganglionic long-term potentiation in prehypertensive and hypertensive stages of spontaneously hypertensive rats depends on GABA modulation. Neural Plasticity 2019 7437894. (https://doi.org/10.1155/2019/7437894)

    • Search Google Scholar
    • Export Citation
  • McCord JM & Fridovich I 1969 The utility of superoxide dismutase in studying free radical reactions I radicals generated by the interaction of sulfite, dimethyl sulfoxide, and oxygen. Journal of Biological Chemistry 244 60566063. (https://doi.org/10.1016/S0021-9258(1863505-7)

    • Search Google Scholar
    • Export Citation
  • Meyer C, McGrath BP & Teede HJ 2005 Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. Journal of Clinical Endocrinology and Metabolism 90 57115716. (https://doi.org/10.1210/jc.2005-0011)

    • Search Google Scholar
    • Export Citation
  • Misra HP & Fridovich I 1972 The role of superoxide-anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry 247 31703175. (https://doi.org/10.1016/S0021-9258(1945228-9)

    • Search Google Scholar
    • Export Citation
  • Mumm H, Kamper-Jørgensen M, Nybo Andersen AM, Glintborg D & Andersen M 2013 Birth weight and polycystic ovary syndrome in adult life: a register-based study on 523,757 Danish women born 1973–1991. Fertility and Sterility 99 777782. (https://doi.org/10.1016/j.fertnstert.2012.11.004)

    • Search Google Scholar
    • Export Citation
  • Münzel T, Camici GG, Maack C, Bonetti NR, Fuster V & Kovacic JC 2017 Impact of oxidative stress on the heart and vasculature: part 2 of a 3-part series. Journal of the American College of Cardiology 70 212229. (https://doi.org/10.1016/j.jacc.2017.05.035)

    • Search Google Scholar
    • Export Citation
  • Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M & Escobar-Morreale HF 2013 Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Human Reproduction Update 19 268288. (https://doi.org/10.1093/humupd/dms059)

    • Search Google Scholar
    • Export Citation
  • Nardo LG, Buckett WM & Khullar V 2003 Determination of the best-fitting ultrasound formulaic method for ovarian volume measurement in women with polycystic ovary syndrome. Fertility and Sterility 79 632633. (https://doi.org/10.1016/s0015-0282(0204801-x)

    • Search Google Scholar
    • Export Citation
  • Ohkawa H, Ohishi N & Yagi K 1979 Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95 351358. (https://doi.org/10.1016/0003-2697(7990738-3)

    • Search Google Scholar
    • Export Citation
  • Orio F, Palomba S & Colao A 2006 Cardiovascular risk in women with polycystic ovary syndrome. Fertility and Sterility 86 (Supplement 1) S20S21. (https://doi.org/10.1016/j.fertnstert.2006.03.003)

    • Search Google Scholar
    • Export Citation
  • Pasquali R 2006 Obesity and androgens: facts and perspectives. Fertility and Sterility 85 13191340. (https://doi.org/10.1016/j.fertnstert.2005.10.054)

    • Search Google Scholar
    • Export Citation
  • Pick E & Keisari Y 1980 A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. Journal of Immunological Methods 38 161170. (https://doi.org/10.1016/0022-1759(8090340-3)

    • Search Google Scholar
    • Export Citation
  • Pietranera L, Bellini MJ, Arévalo MA, Goya R, Brocca ME, Garcia-Segura LM & De Nicola AF 2011 Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: effects of estradiol administration. Neuroscience 174 151159. (https://doi.org/10.1016/j.neuroscience.2010.11.044)

    • Search Google Scholar
    • Export Citation
  • Pinilla L, Rodriguez-Padilla ML, Sanchez-Criado J, Gaytan F & Aguilar E 1992 Mechanism of reproductive deficiency in spontaneously hypertensive rats. Physiology and Behavior 51 99104. (https://doi.org/10.1016/0031-9384(9290209-k)

    • Search Google Scholar
    • Export Citation
  • Pinilla L, Castellano JM, Romero M, Tena-Sempere M, Gaytán F & Aguilar E 2009 Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system. Endocrinology 150 28892897. (https://doi.org/10.1210/en.2008-1381)

    • Search Google Scholar
    • Export Citation
  • Qiu S, Wu C, Lin F, Chen L, Huang Z & Jiang Z 2009 Exercise training improved insulin sensitivity and ovarian morphology in rats with polycystic ovary syndrome. Hormone and Metabolic Research 41 880885. (https://doi.org/10.1055/s-0029-1234119)

    • Search Google Scholar
    • Export Citation
  • Reckelhoff JF, Zhang H & Granger JP 1998 Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 31 435439. (https://doi.org/10.1161/01.hyp.31.1.435)

    • Search Google Scholar
    • Export Citation
  • Roa J & Herbison AE 2012 Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. Endocrinology 153 55875599. (https://doi.org/10.1210/en.2012-1470)

    • Search Google Scholar
    • Export Citation
  • Rodgers RJ, Suturina L, Lizneva D, Davies MJ, Hummitzsch K, Irving-Rodgers HF & Robertson SA 2019 Is polycystic ovary syndrome a 20th century phenomenon? Medical Hypotheses 124 3134. (https://doi.org/10.1016/j.mehy.2019.01.019)

    • Search Google Scholar
    • Export Citation
  • Simão VA, de Almeida Chuffa LG & Cherici Camargo IC 2016 Ovarian sex steroid receptors and sex hormones in androgenized rats. Reproduction 152 545559. (https://doi.org/10.1530/REP-16-0233)

    • Search Google Scholar
    • Export Citation
  • Stener-Victorin E, Padmanabhan V, Walters KA, Campbell RE, Benrick A, Giacobini P, Dumesic DA & Abbott DH 2020 Animal models to understand the etiology and pathophysiology of polycystic ovary syndrome. Endocrine Reviews 41 4153841576. (https://doi.org/10.1210/endrev/bnaa010)

    • Search Google Scholar
    • Export Citation
  • Walters KA, Allan CM & Handelsman DJ 2012 Rodent models for human polycystic ovary syndrome. Biology of Reproduction 86 149, 112. (https://doi.org/10.1095/biolreprod.111.097808)

    • Search Google Scholar
    • Export Citation
  • Wang ET, Ku IA, Shah SJ, Daviglus ML, Schreiner PJ, Konety SH, Dale Williams OD, Siscovick D & Bibbins-Domingo K 2012 Polycystic ovary syndrome is associated with higher left ventricular mass index: the CARDIA women’s study. Journal of Clinical Endocrinology and Metabolism 97 46564662. (https://doi.org/10.1210/jc.2012-1597)

    • Search Google Scholar
    • Export Citation
  • Wu CC & Yen MH 1999 Higher level of plasma nitric oxide in spontaneously hypertensive rats. American Journal of Hypertension 12 476482. (https://doi.org/10.1016/s0895-7061(9900008-4)

    • Search Google Scholar
    • Export Citation
  • Wu C, Jiang F, Wei K, Lin F & Jiang Z 2019 Effects of exercise combined with finasteride on hormone and ovarian function in polycystic ovary syndrome rats. International Journal of Endocrinology 2019 8405796. (https://doi.org/10.1155/2019/8405796)

    • Search Google Scholar
    • Export Citation
  • Wu G, Hu X, Ding J & Yang J 2020 The effect of glutamine on dehydroepiandrosterone-induced polycystic ovary syndrome rats. Journal of Ovarian Research 13 57. (https://doi.org/10.1186/s13048-020-00650-7)

    • Search Google Scholar
    • Export Citation
  • Zhu S, Zhang B, Jiang X, Li Z, Zhao S, Cui L & Chen ZJ 2019 Metabolic disturbances in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis. Fertility and Sterility 111 168177. (https://doi.org/10.1016/j.fertnstert.2018.09.013)

    • Search Google Scholar
    • Export Citation
  • Zuo T, Zhu M & Xu W 2016 Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxidative Medicine and Cellular Longevity 2016 8589318. (https://doi.org/10.1155/2016/8589318)

    • Search Google Scholar
    • Export Citation