CHRONIC SYSTEMIC INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION IN THE ORIGIN OF POLYCYSTIC OVARY SYNDROME


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Abstract

Objective. To carry out a systematic analysis of the current literature on the involvement of chronic systemic inflammation and mitochondrial dysfunction in the etiology and pathogenesis of polycystic ovary syndrome (PCOS) and in the development of its complications. Material and methods. The review included foreign and Russian papers published in the Pubmed journals in the past 10 years on this topic. Results. The paper summarizes the currently known ways of the involvement of mitochondrial dysfunction and chronic systemic and local inflammation in the development of PCOS. It describes possible ways to potentiate oxidative stress and systemic inflammation in PCOS, including in cases of the elevated blood concentrations of free fatty acids and glycation end products, hyperglycemia, hyperleptinemia, and damage accumulation in the mitochondria and mitochondrial DNA. Conclusion. There is accumulating evidence suggesting a positive inverse correlation between systemic inflammation and mitochondrial dysfunction in the origin of PCOS.

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About the authors

Elena Petrovna Khashchenko

Email: khashchenko_elena@mail.ru
postgraduate student 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

Darya V. Tsvirkun

Email: darunyat@gmail.com
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

References

  1. Deligeoroglou E., Vrachnis N., Athanasopoulos N., Iliodromiti Z., Sifakis S., Iliodromiti S. et al. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol. Endocrinol. 2012; 28(12): 974-8. doi: 10.3109/09513590.2012.683082.
  2. 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. doi: 10.3389/ fphys.2016.00124.
  3. Rojas J., Chávez M., Olivar L., Rojas M., Morillo J., Mejias J. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the patophysiologic labyrinth. Int. J. Reprod. Med. 2014; 2014: 1-17. doi: 10.1155/2014/719050.
  4. Sousa S.M., Norman R.J. Metabolic syndrome, diet and exercise. Best Pract. Res. Clin. Obstet. Gynaecol. 2016 Feb 10. pii: S1521-6934(16)00007-9. doi: 10.1016/j.bpobgyn.2016.01.006.
  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. 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.
  7. Oleszczak B., Szablewski L., Pliszka M., Gluszak O., Stopinska-Gluszak U. Transport of deoxy-d-glucose into lymphocytes of patients with polycystic ovary syndrome. Endocrine. 2014; 47(2): 618-24. doi: 10.1007/s12020-014-0174-5.
  8. Diamanti-Kandarakis E., Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr. Rev. 2012; 33(6): 981-1030.
  9. Garg D., Zaher M. Advanced glycation end products: link between diet and ovulatory dysfunction in PCOS? Nutrients. 2015; 7(12): 10129-44.
  10. Dumesic D.A., Oberfield S.E., Stener-Victorin E., Marshall J.C., Laven J.S., Legro R.S. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr. Rev. 2015; 36(5): 487-525. doi: 10.1210/er.2015-1018.
  11. 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.
  12. Murri M., Luque-Ramirez M., Insenser M., Ojeda-Ojeda M., Escobar-Morreale H.F. Circulating 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.
  13. 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.
  14. 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.
  15. Gonzälez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012; 77(4): 300-5. doi: 10.1016/j. steroids.2011.12.003.
  16. Fulghesu A.M., Sanna F., Uda S., Magnini R., Portoghese E., Batetta B. Il-6 serum levels and production is related to an altered immune response in polycystic ovary syndrome girls with insulin resistance. Mediators Inflamm. 2011; 2011: 389317. doi: 10.1155/2011/389317.
  17. Duleba A.J., Dokras A. Is PCOS an inflammatory process? Fertil. Steril. 2012; 97(1): 7-12.
  18. Yang Y., Qiao J., Li R., Li M.Z. Is interleukin-18 associated with polycystic ovary syndrome? Reprod. Biol. Endocrinol. 2011; 9: 7-18. doi: 10.1186/ 1477-7827-9-7.
  19. 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.
  20. Escobar-Morreale H.F., Luque-Ramirez 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.
  21. 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.
  22. Мадянов И.В., Мадянова Т.С. Синдром поликистозных яичников у девочек-подростков: клинико-метаболические особенности и перспективы применения метформина. Практическая медицина. 2010; 43(4): 86-9. [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)]
  23. Victor V.M., Rocha M., Banuls C., Alvarez A., de Pablo C., Sanchez-Serrano M. et al. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. J. Clin. Endocrinol. Metab. 2011; 96(10): 3115-22. doi: 10.1210/ jc.2011-0651.
  24. Gonzalez F., Sia C.L., Shepard M.K., Rote N.S., Minium J. Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome. Hum. Reprod. 2012; 27(12): 3560-8. doi: 10.1093/humrep/des320.
  25. Conway G., Dewailly D., Diamanti-Kandarakis E., Escobar-Morreale H.F., Franks S., Gambineri A. et al. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur. J. Endocrinol. 2014; 171: 1-29. doi: 10.1530/EJE-14-0253.
  26. Niu Z., Lin N., Gu R., Sun Y., Feng Y. Associations between insulin resistance, free fatty acids, and oocyte quality in polycystic ovary syndrome during in vitro fertilization. J. Clin. Endocrinol. Metab. 2014; 99(11): 2269-76. doi: 10.1210/ jc.2013-3942.
  27. Gonzalez 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.
  28. Boden G. Obesity, insulin resistance and free fatty acids. Curr. Opin. Endocrinol. Diabetes Obes. 2011; 18(2): 139-43.
  29. Acosta-Martinez M. PI3K: an attractive candidate for the central integration of metabolism and reproduction. Front. Endocrinol. (Lausanne). 2012; 2: 110-50.
  30. Martin S.S., Qasim A., Reilly M.P. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J. Am. Coll. Cardiol. 2008; 52(15): 1201-10. doi: 10.1016/j.jacc.2008.05.060.
  31. Pertynska-Marczewska M., Diamanti-Kandarakis E., Zhang J., Merhi Z. Advanced glycation end products: a link between metabolic and endothelial dysfunction in polycystic ovary syndrome? Metabolism. 2015; 64(11): 1564-73. doi: 10.1016/j.metabol.2015.08.010.
  32. Isoda K., Folco E., Marwali M.R., Ohsuzu F., Libby P. Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis. Atherosclerosis. 2008; 198(2): 307-12. doi: 10.1016/j.atherosclerosis.2007.10.035.
  33. Diamanti-Kandarakis E., Piperi C., Spina J., Argyrakopoulou G., Papanastasiou L., Bergiele A. et al. Polycystic ovary syndrome: the influence of environmental and genetic factors. Hormones. 2006; 5(1): 17-34.
  34. Thorne J.T., Segal T.R., Chang S., Jorge S., Segars J.H., Leppert P.C. Dynamic reciprocity between cells and their microenvironment in reproduction. Biol. Reprod. 2015; 92(1): 25. doi: 10.1095/biolreprod.114.121368.
  35. Wirth C., Brandt U., Hunte C., Zickermann V. Structure and function of mitochondrial complex I. Biochim. Biophys. Acta. 2016; 1857(7): 902-14. doi: 10.1016/j.bbabio.2016.02.013.
  36. Martinez-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.
  37. Zong W.X., Rabinowitz J.D., White E. Mitochondria and cancer. Mol. Cell. 2016; 61(5): 667-76. doi: 10.1016/j.molcel.2016.02.011.
  38. 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.
  39. Nunnari J., Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012; 148(6): 1145-59. doi: 10.1016/j.cell.2012.02.035.
  40. Yun J., Finkel T. Mitohormesis. Cell Metab. 2014; 19(5): 757-66. doi: 10.1016/j. cmet.2014.01.011.
  41. 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.
  42. Zhao Y., Fu L., Li R., Wang L.N., Yang Y., Liu N.N. et al. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis. BMC Med. 2012; 10: 153-63. doi: 10.1186/1741-7015-10-153.
  43. Kaludercic N., Giorgio V. The dual function of reactive oxygen/nitrogen species in bioenergetics and cell death: the role of ATP synthase. Oxid. Med. Cell. Longev. 2016; 2016: 3869610. doi: 10.1155/2016/3869610.
  44. Ding Y., Zhuo G., Zhang C. The mitochondrial tRNALeu(UUR) A3302G mutation may be associated with insulin resistance in woman with polycystic ovary syndrome. Reprod. Sci. 2016; 23(2): 228-33. doi: 10.1177/1933719115602777.
  45. 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.
  46. Walker M.A., Volpi S., Sims K.B., Walter J.E., Traggiai E. Powering the immune system: mitochondria in immune function and deficiency. J. Immunol. Res. 2014; 2014: 164309. doi: 10.1155/2014/164309.
  47. Konopka A.R., Asante A., Lanza I.R., Robinson M.M., Johnson M.L., Dalla Man C. et al. Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training. Diabetes. 2015; 64(6): 2104-15. doi: 10.2337/db14-1701.

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