Indicators of mitochondrial functioning in adolescent girls with polycystic ovary syndrome with regard to the presence of metabolic disorders and overweight
There is a growing body of evidence supporting the significant role of systemic inflammation and oxidative stress in the genesis of polycystic ovary syndrome (PCOS) in adult patients. The indicators of mitochondrial functioning early in the development of PCOS in adolescence remain little studied. Objective. To study the characteristics of mitochondrial function and systemic inflammation in adolescent girls with different metabolic PCOS phenotypes compared with healthy girls. Subjects and methods. The investigation enrolled 95 girls aged 15 to 17 years inclusive with PCOS according to the Rotterdam criteria. A control group consisted of 30 healthy age-matched regularly cycling girls. All the participants underwent a complete clinical and instrumental examination and estimation of the levels of C-reactive protein, malondialdehyde (MDA), the mitochondrial membrane potential of peripheral blood mononuclear cells (MNC) and MNC fractions with highly polarized mitochondria. The level of glutathione, the ratio of its oxidized (GSSH) to reduced (GSH) forms (GSSR/GSH), and the enzymatic activity of catalase, glutathione reductase and glutathione peroxidase were determined. Results. As compared with the healthy girls, the normal weight patients with PCOS in the absence of metabolic abnormalities (PCOS-MA_NW) had a lower concentration of MDA, decreased activity of the antioxidant enzyme glutathione reductase, a higher level of the reduced form of the antioxidant glutathione and its ratio to the oxidized form, and a higher percentage of MNCs with highly polarized mitochondria (p <0.05 for all indicators). The patients with PCOS-MA_NW showed lower C-reactive protein (CRP) and MDA levels than those with PCOS-MA_OW) (p < 0.05). The girls with PCOS-MA_OW) had higher levels of CRP and enhanced glutathione reductase and MDA activities than those with PCOS-MA_NW (p < 0.05). Comparison of the girls PCOS+MA_OW) and those with PCOS+MA_NW revealed significant increases in the levels of CRP and MDA and the activity of glutathione reductase (p < 0.05). The girls with PCOS-MA_OW had a higher MDA level than those with PCOS+MA_NW (p < 0.05). As compared with the healthy girls, the PCOS+MA_NW group had a lower level of MDA, an elevated concentration of reduced glutathione, and lower activity of glutathione reductase (p < 0.05). The found characteristics are confirmed by a correlation analysis and by the results of two-factor analysis of variance. Conclusion. An adaptive mechanism for reducing the manifestations of oxidative stress and systemic inflammation with the high coupling of mitochondrial respiration and the level of antioxidant protection is realized in the normal weight adolescents with PCOS. The manifestations of oxidative stress, which are mediated by mitochondrial uncoupling due to impaired cholesterol and glucose metabolism, are pronounced, which is enhanced by the addition of carbohydrate metabolic disturbances in the overweight adolescents with PCOS. Mitochondrial dysfunction is associated with the activation of systemic inflammatory response in the overweight adolescents with PCOS in the presence of insulin resistance.Khashchenko E.P., Sukhanova Yu.A., Pyataeva S.V., Volodina M.A., Tarasova N.V., Tsvirkun D.V., Uvarova E.V., Vysokikh M.Yu.
Keywords
polycystic ovary syndrome
insulin resistance
systemic inflammation
mitochondrial dysfunction
glutathione
glutathione reductase
glutathione perioxidase
Supplementary Materials
- Table 1. Indicators of blood lipid profile, oral glucose tolerance th th test results and, VAI index and C-reactive protein levels in adolescents with polycystic ovary syndrome om considering metabolic disorders and obesity
- Table 2. energization of mitochondria in the mononuclear cell fraction, the parameters of oxidative stress and antioxidant defense in the peripheral blood in adolescents with polycystic ovary syndrome based on metabolic disorders and obesity
- Drawing. Two-factor ANOVA interaction factors obesity and metabolic disorders in the presence of malondialdehyde level in adolescents with polycystic ovary syndrome
References
1. El Hayek S., Bitar L., Hamdar L.H., Mirza F.G., Daoud G. Poly cystic ovarian syndrome: an updated overview. Front. Physiol. 2016; 7: 124. Published online 2016; Apr 5. doi: 10.3389/fphys.2016.00124.
2. Rojas J., Chávez M., Olivar L., Rojas M., Morillo J., Mejías J. et al. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int. J. Reprod. Med. 2014; 2014: 719050. doi: 10.1155/2014/719050.
3. Sousa S.M., Norman R.J. Metabolic syndrome, diet and exercise. Best Pract. Res. Clin. Obstet. Gynaecol. 2016; 37: 140-51. doi: 10.1016/j.bpobgyn.2016.01.006.
4. Chernukha G.Ye., Blinova I.V., Kuprashvili M.I. Endocrine and metabolic characteristics of patients with different phenotypes of polycystic ovary syndrome. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2011; (2): 70-6. (in Russian)
5. Goodman N.F., Cobin R.H., Futterweit W., Glueck J.S., Legro R.S., Carmina E. American association of clinical endocrinologists, american college of endocrinology, and androgen excess and pcos society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome- part 1. Endocr. Pract. 2015; 21(11): 1291-300. doi: 10.4158/EP15748.DSC.
6. Turan V., Sezer E.D., 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(2): 119-23. doi: 10.1016/j.jpag.2014.05.003.
7. Murri M., Luque-Ramírez M., Insenser M., Ojeda-Ojeda M., Escobar-Morreale H.F. irculating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systemic review and meta-analysis. Hum. Reprod. Update. 2013; 19(3): 268-88. doi: 10.1093/humupd/dms059.
8. Zuo T., Zhu M., Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxid. Med. Cell. Longev. 2016; 2016: 8589318. doi: 10.1155/2016/8589318.
9. Tao T., Li S., Zhao A., Zhang Y., Liu W. Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome. Eur. J. Endocrinol. 2012; 167(5): 705-13. doi: 10.1530/EJE-12-0340.
10. Repaci A., Gambineri A., Pasquali R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol. Cell. Endocrinol. 2011; 335(1): 30-41. doi: 10.1016/j.mce.2010.08.002.
11. Sathyapalan T., Atkin S.L. Mediators of inflammation in polycystic ovary syndrome in relation to adiposity. Mediators Inflamm. 2010; 2010: 758656. doi: 10.1155/2010/758656.
12. Zorov D.B., Juhaszova M., Sollott S.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 2014; 94(3): 909-50. doi: 10.1152/physrev.00026.2013.
13. Amato M.C., Guarnotta V., Forti D., Donatelli M., Dolcimascolo S., Giordano C. Metabolically healthy polycystic ovary syndrome (MH-PCOS) and metabolically unhealthy polycystic ovary syndrome (MU-PCOS): a comparative analysis of four simple methods useful for metabolic assessment. Hum. Reprod. 2013; 28(7): 1919-28. doi: 10.1093/humrep/det105.
14. Jentzsch A.M., Bachmann H., Fürst P., Biesalski H.K. Improved analysis of malondialdehyde in human body fluids. Free Radic. Biol. Med. 1996;20(2): 251-6.
15. Giustarini G., Dalle-Donne I., Milzani A., Fanti P., Rossi R. Analysis of GSH and GSSG after derivatization with N-ethylmaleimide. Nat. Protoc. 2013; 8(9): 1660-9. doi: 10.1038/nprot.2013.095.
16. Escobar-Morreale H.F., Luque-Ramírez M., González F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and meta-analysis. Fertil Steril. 2011; 95(3): 1048-58. doi: 10.1016/j.fertnstert.2010.11.036.
17. Lee H., Oh J.Y., Sung Y.A. Adipokines, insulin-like growth factor binding protein-3 levels, and insulin sensitivity in women with polycystic ovary syndrome. Korean J. Intern. Med. 2013; 28(4): 456-63. doi: 10.3904/kjim.2013.28.4.456.
18. Madyanov I.V., Madyanova T.S. Polycystic ovary syndrome in adolescent girls: clinical and metabolic characteristics and prospects of metformin. Prakticheskaya meditsina/Practical Medicine. 2010; 43(4): 86-9. (in Russian)
19. 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.
20. Prasad S., Tiwari M., Pandey A.N., Shrivastav T.G., Chaube S.K. Impact of stress on oocyte quality and reproductive outcome. J. Biomed. Sci. 2016; 23: 36. doi: 10.1186/s12929-016-0253-4.
21. Gupta S., Ghulmiyyah J., Sharma R., Halabi J., Agarwal A. Power of proteomics in linking oxidative stress and female infertility. Biomed. Res. Int. 2014; 2014: 916212. doi: 10.1155/2014/916212.
22. Martínez-Reyes I., Diebold L.P., Kong H., Schieber M., Huang H., Hensley C.T. et al. TCA cycle and mitochondrial membrane potential are necessary for diverse biological functions. Mol. Cell. 2016; 61(2): 199-209. doi: 10.1016/j.molcel.2015.12.002.
23. Kim J., Wei Y., Sowers J.R. Role of mitochondrial dysfunction in insulin resistance. Circ. Res. 2008; 102(4): 401-14. doi: 10.1161/CIRCRESAHA.107.165472.
24. Wenceslau C.F., McCarthy C.G., Szasz T., Spitler K., Goulopoulou S., Webb R.C.; Working Group on DAMPs in Cardiovascular Disease. Mitochondrial damage-associated molecular patterns and vascular function. Eur. Heart J. 2014; 35(18): 1172-7. doi: 10.1093/eurheartj/ehu047.
25. González F. Nutrient-induced inflammation in polycystic ovary syndrome: role in the development of metabolic aberration and ovarian dysfunction. Semin. Reprod. Med. 2015; 33(4): 276-86. doi: 10.1055/s-0035-1554918.
26. Boden G. Obesity, insulin resistance and free fatty acids. Curr. Opin. Endocrinol. Diabetes Obes. 2011; 18(2): 139-43.
Received 16.12.2017
Accepted 23.12.2017
About the Authors
Khashchenko Elena Petrovna, gynecologist at the Department of Pediatric Gynecology, Research Center of Obstetrics, Gynecology, and Perinatology,Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: khashchenko_elena@mail.ru
Sukhanova Yuliia A., research fellow at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: suhanova_julia@hotmail.com
Pyataeva Sofia V., PhD, researcher at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: biosonya@gmail.com
Volodina Maria A., PhD, researcher at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: m_volodina@oparina4.ru
Tarasova Nadejda V., PhD, researcher at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: n_tarasova@oparina4.ru
Tsvirkun Darya V., PhD, researcher at mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: darunyat@gmail.com
Uvarova Elena V., MD PhD, Professor, Head of the Department of Pediatric Gynecology, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: elena-uvarova@yandex.ru
Vysokikh Mikhail Yu., PhD, Head of mitochondrial medicine research group, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia,
Head of aging molecular mechanism group, A.N. Belozersky Research Institute of Physicochemical Biology.
117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: m_vysokikh@oparina4.ru
For citations: Khashchenko E.P., Sukhanova Yu.A., Pyataeva S.V., Volodina M.A.,
Tarasova N.V., Tsvirkun D.V., Uvarova E.V., Vysokikh M.Yu. Indicators of mitochondrial functioning in adolescent girls with polycystic ovary syndrome with regard to the presence of metabolic disorders and overweight. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (7): 104-13. (in Russian)
http://dx.doi.org/10.18565/aig.2017.7.104-13
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