Influence of obesity on sperm DNA fragmentation index and outcomes of IVF programs

The reduction of the birth rates in the developed countries and increase in the frequency of male infertility stimulate the extensive investigations for the factors that negatively affect the reproductive system of the men and causing their infertility. The excessive body weight and obesity in the men of the reproductive age can promote the development of infertility. One of the mechanisms by which excess fat tissue has a negative impact on male fertility is disturbance of spermatogenesis. The authors aggregate scientific publications concerning the macroscopic and ultrastructural disturbances of spermatogenesis in men with obesity. We present the results of the study conducted at the Department of ART Endocrinology Research Center, targeted at the revelation of the relationship of body mass index of men of reproductive age, semen parameters, sperm DNA fragmentation index, as well as the influence of body mass index on outcomes of in vitro fertilization programs.

1. Витязева И.И., Алташина М.В., Трошина Е.А. “Влияние нарушений жирового обмена на фертильность мужчин репродуктивного возраста и эффективность программ ЭКО”. //Проблемы эндокринологии. 2014;60:5:34-42. [Vityazeva II, Altashina MV, Troshina EA. The influence of disordered fat metabolism on male fertility at the reproductive age and the effectiveness of the ECF programs. Probl Endokrinol (Mosk). 2014;60(5):34-42. (In Russ.)]. doi: 10.14341/probl201460534-42.

2. Божедомов В.А., Громенко Д.С., Ушакова И.В. и др. “Причины оксидативного стресса сперматозоидов”. //Проблемы репродукции. 2008;6:67-73. [Bozhedomov VA, Gromenko DS, Ushakova IV, et al. Prichiny oksidativnogo stressa spermatozoidov. Problemy reproduktsii. 2008;(6):67-73. (In Russ.)].

3. Брагина Е.Е., Замятнина В.А., Бочарова Е.Н., и др. “Количественное ультраструктурное исследование хроматина сперматозоидов при нарушении фертильности”. // Андрология и генитальная хирургия. 2009;1:44-49. [Bragina EE, Zamyatnina VA, Bocharova EN, et al. Quantitative ultrastructural research research of spermatozoon from patients with fertility infringement. Andrologiya i genital’naya khirurgiya. 2009;(1):44-49. (In Russ.)].

4. Singh K, Jaiswal D. Human male infertility: a complex multifactorial phenotype. Reprod Sci. 2011;18(5):418-425. doi: 10.1177/1933719111398148.

5. Cabler S, Agarwal A, Flint M, du Plessis SS. Obesity: modern man’s fertility nemesis. Asian J Androl. 2010;12(4):480-489. doi: 10.1038/aja.2010.38.

6. Sallmén M, Sandler DP, Hoppin JA, et al. Reduced Fertility Among Overweight and Obese Men. Epidemiology. 2006;17(5):520-523. doi: 10.1097/01.ede.0000229953.76862.e5.

7. Palmer NO, Bakos HW, Fullston T, Lane M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012;2(4):253-263. doi: 10.4161/spmg.21362.

8. Sunderam S, Chang J, Flowers L, et al. Assisted reproductive technology surveillance—United States, 2006: Department of Health and Human Services, Centers for Disease Control and Prevention. 2009.

9. Evgeni E, Charalabopoulos K, Asimakopoulos B. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J Reprod Infertil. 2014;15(1):2-14. PMID: 24696791.

10. Боголюбов С.В., Витязева И.И., Макарова Н.П., Львова А.Г. “Клиническое ведение пациентов с тератозооспермией в циклах вспомогательных репродуктивных технологий”. //Доктор.Ру. 2009;6:34-38. [Bogolyubov SV, Vityazeva II, Makarova NP, L’vova AG. Klinicheskoe vedenie patsientov s teratozoospermiey v tsiklakh vspomogatel’nykh reproduktivnykh tekhnologiy. Doktor.Ru. 2009;(6):34-38. (In Russ.)].

11. Gonzalez-Marin C, Gosalvez J, Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci. 2012;13(11):14026-14052. doi: 10.3390/ijms131114026.

12. Sharlip ID, Jarow JP, Belker AM, et al. Best practice policies for male infertility. Fertil Steril. 2002;77(5):873-882. PMID: 12009338.

13. Niederberger C. WHO manual for the standardized investigation, diagnosis and management of the infertile male. Elsevier. 2001.

14. Kashir J, Jones C, Lee HC, et al. Loss of activity mutations in phospholipase C zeta (PLCzeta) abolishes calcium oscillatory ability of human recombinant protein in mouse oocytes. Hum Reprod. 2011;26(12):3372-3387. doi: 10.1093/humrep/der336.

15. Брагина Е.Е., Замятнина В.А., Гаврилов Ю.А., и др. “Упаковка хроматина и фрагментация ДНК: два типа нарушений наследственного материала сперматозоидов”. //Медицинская генетика. 2009;8:10:29-35. [Bragina EE, Zamjatnina VA, Gavrilov JA, et al. Chromatin Packing and DNA fragmentation: Two types of infringements of a sperm hereditary material. Meditsinskaya genetika. 2009;8(10):29-35. (In Russ.)].

16. Evenson DP, Larson KL, Jost LK. Sperm Chromatin Structure Assay: Its Clinical Use for Detecting Sperm DNA Fragmentation in Male Infertility and Comparisons With Other Techniques. J Androl. 2002;23(1):25-43. doi: 10.1002/j.1939-4640.2002.tb02599.x.

17. Evenson DP. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14(4):1039-1049. doi: 10.1093/humrep/14.4.1039.

18. Spanò M, Bonde JP, Hjøllund HI, et al. Sperm chromatin damage impairs human fertility. Fertil Steril. 2000;73(1):43-50. doi: 10.1016/s0015-0282(99)00462-8.

19. Светлаков А.В., Шеина Ю.И., Еремеев А.В., Серебренникова О.А. “Анализ фрагментации ДНК сперматозоидов, как независимый критерий качества эякулята в практике Красноярского центра репродуктивной медицины”. //Андрология и генитальная хирургия. 2011;2:126. [Svetlakov AV, Sheina YI, Eremeev AV, Serebrennikova OA. Analiz fragmentatsii DNK spermatozoidov, kak nezavisimyy kriteriy kachestva eyakulyata v praktike Krasnoyarskogo tsentra reproduktivnoy meditsiny. Andrologiya i genital’naya khirurgiya. 2011;(2):126. (In Russ.)].

20. Dupont C, Faure C, Sermondade N, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15(5):622-625. doi: 10.1038/aja.2013.65.

21. Swan SH, Elkin EP, Fenster L. The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996. Environ Health Perspect. 2000;108(10):961-966. PMID: 11049816.

22. Дедов И.И., Мельниченко Г.А. (ред.). “Эндокринология. Национальное руководство». М.: ГЭОТАР-Медиа. 2009;475. [Dedov II, Mel’nichenko GA, (eds). Endocrinology. National guidelines. Moscow: GEOTAR-Media. 2009. (In Russ.)].

23. Aitken RJ, Baker MA. Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol. 2006;250(1-2):66-69. doi: 10.1016/j.mce.2005.12.026.

24. Shamsi MB, Kumar R, Dada R. Evaluation of nuclear DNA damage in human spermatozoa in men opting for assisted reproduction. Indian J Med Res. 2008;127(2):115-123. PMID: 18403788.

25. Practice Committee of the American Society for Reproductive M. The clinical utility of sperm DNA integrity testing: a guideline. Fertil Steril. 2013;99(3):673-677. doi: 10.1016/j.fertnstert.2012.12.049.

26. Zini A, Meriano J, Kader K, et al. Potential adverse effect of sperm DNA damage on embryo quality after ICSI. Hum Reprod. 2005;20(12):3476-3480. doi: 10.1093/humrep/dei266.

27. Dupont C, Faure C, Sermondade N, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15(5):622-625. doi: 10.1038/aja.2013.65.

28. Fariello RM, Pariz JR, Spaine DM, et al. Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. BJU Int. 2012;110(6):863-867. doi: 10.1111/j.1464-410X.2011.10813.x.

29. MacDonald AA, Stewart AW, Farquhar CM. Body mass index in relation to semen quality and reproductive hormones in New Zealand men: a cross-sectional study in fertility clinics. Hum Reprod. 2013;28(12):3178-3187. doi: 10.1093/humrep/det379.

30. Hultman CM, Sandin S, Levine SZ, et al. Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Mol Psychiatry. 2010;16(12):1203-1212. doi: 10.1038/mp.2010.121.

31. Agarwal A, Damer M. Sperm chromatin assessment. Textbook of assisted reproduction techniques. Taylor & Francis Group (London). 2004.

32. Chohan KR, Griffin JT, Lafromboise M, et al. Comparison of Chromatin Assays for DNA Fragmentation Evaluation in Human Sperm. J Androl. 2006;27(1):53-59. doi: 10.2164/jandrol.05068.

33. Muriel L. Structure of human sperm DNA and background damage, analysed by in situ enzymatic treatment and digital image analysis. Mol Hum Reprod. 2004;10(3):203-209. doi: 10.1093/molehr/gah029.

34. Rivero MT, Vazquez-Gundin F, Muriel L, et al. Patterns of DNA migration in two-dimensional single-cell gel electrophoresis analyzed by DNA breakage detection-fluorescence in situ hybridization. Environ Mol Mutagen. 2003;42(3):223-227. doi: 10.1002/em.10187.

35. Шеина Ю.И., Зайцева Т.А, Махалова Н.А., и др. “Анализ фрагментации ДНК в сперматозоидах с помощью окраски акридиновым оранжевым у пациентов с бесплодием”. //Проблемы репродукции. 2012;5:74-79. [Sheina II, Zaĭtseva TA, Makhalova NA, et al. The analysis of sperm DNA fragmentation in infertility patients with the help of acridine orange staining. Problemy reproduktsii. 2012;(5):74-79. (In Russ.)].

36. Larson KL, DeJonge CJ, Barnes AM, et al. Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod. 2000;15(8):1717-1722. doi: 10.1093/humrep/15.8.1717.

37. Fernández JL, Vázquez-Gundı́n F, Rivero MT, et al. DBD-FISH on Neutral Comets: Simultaneous Analysis of DNA Single- and Double-Strand Breaks in Individual Cells. Exp Cell Res. 2001;270(1):102-109. doi: 10.1006/excr.2001.5328.