On the pathogenesis of reproductive disorders in women with obesity

Vedzizheva E.R., Kuznetsova I.V., Uspenskaya Yu.B., Gitel E.P., Vasilyeva I.V.

Research Department of Women’s Health, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow 119991, Bolshaya Pirogovskaya str. 2, bld. 4, Russia
Objective. To carry out a systematic analysis of the data available in the current literature on the role of adipokines in reproductive dysfunction in obese women.
Material and methods. For analysis, foreign and Russian works published in the past 15 years were sought for in the international citation system Pubmed.
Results. The modern theories of the mechanism of reproductive disorders in obese women were described; the key factors of impact of adipose tissue on fertility were described. The importance of regulation of the body’s metabolic processes in restoring fertility and preparing women for pregnancy was highlighted.
Conclusion. Most current studies often show conflicting and ambiguous results, which leads to the need for further research.

Keywords

adipose tissue
overweight
obesity
female reproductive health
adipokines

References

1. Crujeiras A.B., Casanueva F.F. Obesity and the reproductive system disorders: epigenetics as a potential bridge. Hum. Reprod. Update. 2014; 34(5): 123-36.

2. Kosygina A.V. Novel in pathogenesis of obesity: adipokines – fat tissue hormones. Problemy endokrinologii. 2009; 55(1): 44-50. (in Russian)

3. Bohler H. Jr., Mokshagundam S., Winters S.J. Adipose tissue and reproduction in women. Fertil. Steril. 2010; 94(3): 795-825.

4. Motta A.B. The role of obesity in the development of polycystic ovary syndrome. Curr. Pharm. Des. 2012; 18(17): 2482-91.

5. Michalakis K., Mintziori G., Kaprara A. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism. 2013; 62(4): 457-78.

6. Budak E., Fernandez Sanchez M., Bellver J., Cerveró A., Simón C., Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3–36 with the reproductive system. Fertil. Steril. 2006; 85(6): 1563-81.

7. Heidemann C., Sun Q., van Dam R.M., Meigs J.B., Zhang C., Tworoger S.S. et al. Total and highmolecular- weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann. Intern. Med. 2008; 149(5): 307-16.

8. Tomas E., Tsao T.S., Saha A.K., Murrey H.E., Zhang C.C., Itani S.I. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl. Acad. Sci. USA. 2002; 99(25): 16309-13.

9. Jungheim E.S., Travieso J.L., Hopeman M.M. Weighing the impact of obesity on female reproductive function and fertility. Nutr. Rev. 2013; 71: 3-8.

10. Chabrolle C., Tosca L., Rame C., Lecomte P., Royère D., Dupont J. Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells. Fertil. Steril. 2009; 92(6): 1988-96. doi: 10.1016/j.fertnstert.2008.09.008.

11. Toulis K.A., Goulis D.G., Farmakiotis D., Georgopoulos N.A., Katsikis I., Tarlatzis B.C. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum. Reprod. Update. 2009; 15(3): 297-307. doi: 10.1093/humupd/dmp006.

12. Zhang J., Zhou L., Tang L., Xu L. The plasma level and gene expression of resistin in polycystic ovary syndrome. Gynecol. Endocrinol. 2011; 27(12): 982-7.

13. Stofkova A. Resistin and visfatin: regulators of insulin sensitivity, inflammation and immunity. Endocr. Regul. 2010; 44(1): 25-36.

14. Ogbuji Q.C. Obesity and reproductive performance in women. Afr. J. Reprod. Health. 2010; 14(3): 143-51.

15. Blum C.A., Muller B., Huber P., Kraenzlin M., Schindler C., De Geyter C. et al. Low-grade inflammation and estimates of insulin resistance during the menstrual cycle in lean and overweight women. J. Clin. Endocrinol. Metab. 2009; 90(6): 3230-5.

16. Mantzoros C.S. Leptin in relation to the lipodystrophyassociated metabolic syndrome. Diabetes Metab J. 2012; 36(3): 181-9.

17. Donato J.Jr., Cravo R.M., Frazão R., Elias C.F. Hypothalamic sites of leptin action linking metabolism and reproduction. Neuroendocrinology. 2011; 93(1): 9-18. doi: 10.1159/000322472.

18. Kelesidis T., Mantzoros C.S. The emerging role of leptin in humans. Pediatr. Endocrinol. Rev. 2006; 3: 239-48.

19. Chang Y.H., Chang D.M., Lin K.C., Shin S.J., Lee Y.J. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab. Res. Rev. 2011; 27(6): 515-27.

20. Gul O.O., Cander S., Gul B., Açıkgoz E., Sarandol E., Ersoy C. Evaluation of insulin resistance and plasma levels for visfatin and resistin in obese and non-obese patients with polycystic ovary syndrome. Eur. Cytokine Netw. 2015; 26(4): 73-8.

21. Tsouma I., Kouskouni E., Demeridou S., Boutsikou M., Hassiakos D., Chasiakou A. et al. Gynecol. Endocrinol. 2014; 30(7): 516-9. doi: 10.3109/09513590.2014.896896.

22. Güdücü N., İşçi H., Görmüş U., Yiğiter A.B., Dünder I. Serum visfatin levels in women with polycystic ovary syndrome. Gynecol. Endocrinol. 2012; 28(8): 619-23. doi: 10.3109/09513590.2011.650749.

23. Ozkaya M., Cakal E., Ustun Y., Engin-Ustun Y. Effect of metformin on serum visfatin levels in patients with polycystic ovary syndrome. Fertil. Steril. 2010; 93(3): 880-4.

24. Spanos N., Tziomalos K., Macut D., Koiou E., Kandaraki E.A., Delkos D. et al. Adipokines, insulin resistance and hyperandrogenemia in obese patients with polycystic ovary syndrome: cross-sectional correlations and the effects of weight loss. Obes. Facts. 2012; 5(4): 495-504. doi: 10.1159/000341579.

25. Verbovoy A., Solomonova E. The level of omentin and other adipokines in serum of patients with impaired glucose tolerance. Vrach. 2012; 11: 79-81. (in Russian)

26. Yang H.Y., Ma Y., Lu X.H., Liang X.H., Suo Y.J., Huang Z.X. et al. The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome. Ann. Endocrinol.(Paris). 2015; 76(5): 620-7. doi: 10.1016/j.ando.2015.08.002.

27. Mahde A., Shaker M., Al-Mashhadani Z. Study of omentin1 and other adipokines and hormones in PCOS patients. Oman Med. J. 2009; 24(2):108-18.

28. Pandey G.K., Balasubramanyam J., Balakumar M., Deepa M., Anjana R.M., Abhijit S. et al. Altered circulating levels of retinol binding protein 4 and transthyretin in relation to insulin resistance, obesity, and glucose intolerance in asian indians. Endocr. Pract. 2015; 21(8): 861-9. doi: 10.4158/EP14558.OR.

29. Volek J.S., Phinney S.D., Forsythe C.E., Quann E.E., Wood R.J., Puglisi M.J. et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids. 2009; 44(4): 297-309. doi: 10.1007/s11745-008-3274-2.

30. Jia J., Bai J., Liu Y., Yin J., Yang P., Yu S. et al. Association between retinol-binding protein 4 and polycystic ovary syndrome: a meta-analysis. Endocr. J. 2014; 61(10): 995-1002.

31. Wickenheisser J.K., Nelson-Degrave V.L., McAllister J.M. Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2005; 90(3): 1720-7.

32. Cakal E., Ozkaya M., Engin-Ustun Y., Ustun Y. Serum lipocalin-2 as an insulin resistance marker in patients with polycystic ovary syndrome. J. Endocrinol. Invest. 2011; 34(2): 97-100.

33. Koiou E., Tziomalos K., Katsikis I., Kandaraki E.A., Kalaitzakis E., Delkos D. et al. Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome. Gynecol. Endocrinol. 2012; 28(1): 20-4. doi: 10.3109/09513590.2011.588745.

34. Bozaoglu K., Bolton K., McMillan J., Zimmet P., Jowett J., Collier G. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology. 2007; 148(10): 4687-94.

35. Tan B.K., Chen J., Farhatullah S., Adya R., Kaur J., Heutling D. et al. Insulin and metformin regulate circulating and adipose tissue chemerin. Diabetes. 2009; 58(9): 1971-7. doi: 10.2337/db08-1528.

36. Huang R., Yue J., Sun Y., Zheng J., Tao T., Li S. et al. Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume. Clin. Chim. Acta. 2015; 450: 366-9. doi: 10.1016/j.cca.2015.09.015.

37. Angelidis G., Dafopoulos K., Messini C.I., Valotassiou V., Georgoulias P., Messinis I.E. Ghrelin: new insights into female reproductive system-associated disorders and pregnancy. Reprod. Sci. 2012; 19(9): 903-10. doi: 10.1177/1933719112443880.

38. Geliebter A., Carnell S., Gluck M.E. Cortisol and ghrelin concentrations following a cold pressor stress test in owerweight individuals with and without Night Eating. Int. J. Obes.(London). 2013; 37(8): 1104-8. doi: 10.1038/ijo.2012.166.

39. Szczepankiewicz D., Skrzypski M., Pruszynska-Oszmalek E., Zimmermann D., Andralojc K., Kaczmarek P. et al. Importance of ghrelin in hypothalamus-pituitary axis on growth hormone release during normal pregnancy in the rat. J. Physiol. Pharmacol. 2010; 61(4): 443-9.

40. Roa J., Tena-Sempere M. Connecting metabolism and reproduction: Roles of central energy sensors and key molecular mediators. Mol. Cell. Endocrinol. 2014; 397(1-2): 4-14. doi: 10.1016/j.mce.2014.09.027.

41. Taylor P.D., Samuelsson A.M., Poston L. Maternal obesity and the developmental programming of hypertension: a role for leptin. Acta Physiol.(Oxford). 2014; 210(3): 508-23. doi: 10.1111/apha.12223.

42. Freeman E.W., Gracia C.R., Sammel M.D., Lin H., Lim L.C., Strauss J.F. 3rd. Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil. Steril. 2007; 87(1): 101-6.

43. Metwally M., Li T.C., Ledger W.L. The impact of obesity on female reproductive function. Obes. Rev. 2007; 8(6): 515-23.

44. De Pergola G., Tartagni M., d’Angelo F., Centoducati C., Guida P., Giorgino R. Abdominal fat accumulation, and not insulin resistance, is associated to oligomenorrhea in non-hyperandrogenic overweight/obese women. J. Endocrinol. Invest. 2009; 32(2): 98-101.

45. Chavarro J.E., Rich-Edwards J.W., Rosner B.A. A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility. Eur. J.Clin. Nutr. 2009; 63(1): 78-86.

46. Fischer-Posovszky P., Wabitsch M., Hochberg Z. Endocrinology of adipose tissue—an update. Horm. Metab. Res. 2007; 39(5): 314-21.

47. Jungheim E.S., Travieso J.L., Carson K.R. Obesity and reproductive function. Obstet. Gynecol. Clin. North Am. 2012; 39(4): 479-93. doi: 10.1016/j.ogc.2012.09.002.

48. De Leo V., Musacchio M.C., Piomboni P., Di Sabatino A., Morgante G. The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011; 157(1): 63-6.

49. Boeing H. Obesity and cancer—the update 2013. Best Pract. Res. Clin. Endocrinol. Metab. 2013; 27(2): 219-27. doi: 10.1016/j.beem.2013.04.005.

50. Rumyanceva S.A., Oganov R.G., Stupin V.A., Silina E.V., Orlova A.S., Bolevich S.B., Afanasev V.V., Kabaeva E.N., Volik S.A. Problems and prospects of intermediary metabolism correction in patients with vascular comorbidity. Racional’naja farmakoterapija v kardiologii. 2013; 9(3): 316-322. (in Russian)

Received 12.12.2016

Accepted 23.12.2016

About the Authors

Vedzizheva Elina Ruslanovna, graduate student at Research Department of Women’s Health, I.M. Sechenov First Moscow State Medical University,
Ministry of Health of Russia. 119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2, bld. 4. E-mail: ishu2009@mail.ru
Kuznetsova Irina Vsevolodovna, MD, professor, chief researcher at Research Department of Women’s Health, I.M. Sechenov First Moscow State Medical University,
Ministry of Health of Russia. 119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2, bld. 4. E-mail: ms_smith@list.ru
Uspenskaya Yulia Borisovna, PhD, leading researcher at Research Department of Women’s Health, I.M. Sechenov First Moscow State Medical University,
Ministry of Health of Russia. 119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2, bld. 4
Gitel Evgenij Pavlovich, PhD, associate director on laboratory technologies at I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.
119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2, bld. 4
Vasilyeva Irina Vadimovna, senior researcher at Research Department of Women’s Health, I.M. Sechenov First Moscow State Medical University,
Ministry of Health of Russia. 119991, Russia, Moscow, Bolshaya Pirogovskaya str. 2, bld. 4

For citations: Vedzizheva E.R., Kuznetsova I.V., Uspenskaya Yu.B., Gitel E.P., Vasilyeva I.V.
On the pathogenesis of reproductive disorders in women with obesity.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (6): 18-24.(in Russian)
http://dx.doi.org/10.18565/aig.2017.6.18-24

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.