Мелатонин и мужское бесплодие, вызванное окислительным стрессом

Главная

Статья в Elpub

РУС ENG

Андрология и генитальная хирургия. 2024; 25: 15-23

Мелатонин и мужское бесплодие, вызванное окислительным стрессом

Белый Л. Е.

https://doi.org/10.62968/2070-9781-2024-25-3-15-23

Аннотация

Среди пар, неспособных зачать ребенка, бесплодие частично или полностью объясняется мужским фактором примерно в 50% случаев. При рутинном обследовании этиология мужского бесплодия остается неопределенной у 30–50% пациентов. Одним из частых этиологических факторов мужского бесплодия является окислительный стресс, который фактически представляет собой дисбаланс между выработкой активных форм кислорода и механизмами антиоксидантной защиты организма. Сегодня предложен термин «мужское бесплодие, обусловленное окислительным стрессом» (male oxidative stress infertility) как новый дескриптор для бесплодных мужчин с сочетанием аномальных характеристик спермы и окислительного стресса. В этой связи наряду с использованием традиционных антиоксидантов необходим поиск новых молекул для борьбы с окислительным стрессом у бесплодных мужчин. Перспективной стратегией выглядит использование в качестве антиоксиданта мелатонина – гормона, секретируемого шишковидной железой.
В обзоре рассмотрены антиоксидантные эффекты метаболического каскада мелатонина. Приведены результаты иследований, доказывающих связь между уровнем мелатонина в семенной плазме и мужской фертильностью. Представлены новые научные данные, касающиеся защитного потенциала мелатонина против окислительного стресса, вызванного различными метаболическими нарушениями, противораковой химио- и лучевой терапией и другими патогенетическими состояниями и негативными воздействиями. Проанализированы исследования, результаты которых демонстрируют перспективы использования мелатонина для защиты сперматозоидов от окислительного повреждения при реализации вспомогательных репродуктивных технологий. Подведены промежуточные итоги исследований, посвященных возможности применения мелатонина в качестве пищевой добавки у инфертильных мужчин.

Список литературы

1. Inhorn M.C., Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21(4):411-426. DOI: 10.1093/humupd/dmv016

2. Rutstein S.O., Shah I.H. ORC Macro; World Health Organization. Infecundity, infertility, and childlessness in developing countries. Calverton: World Health Organization; 2004.

3. Kumar N., Singh A.K. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015;8(4):191-196. DOI: 10.4103/0974-1208.170370

4. Agarwal A., Parekh N., Panner Selvam M.K., et al. Male Oxidative Stress Infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37(3):296-312. DOI: 10.5534/wjmh.190055

5. Наумов Н.П., Щеплев П.А., Полозов В.В. Роль антиоксидантов в профилактике мужского бесплодия. Андрология и генитальная хирургия 2019;20(1):22–29. DOI: 10.17650/2070-9781-2019-20-1-22-29.

6. Patel A.S., Leong J.Y., Ramasamy R. Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: A systematic review. Arab J Urol. 2017;16(1):96-102. DOI: 10.1016/j.aju.2017.10.005

7. World Health Organization. WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple. 2000, Cambridge University Press: Cambridge.

8. Takalani N.B., Monageng E.M., Mohlala K. et al. Role of oxidative stress in male infertility. Reprod Fertil. 2023;4(3):e230024. DOI: 10.1530/RAF-23-0024

9. Гвасалия Б.Р., Исаева А.В., Бабаев М.У. Место антиоксидантов в терапии мужского бесплодия. Андрология и генитальная хирургия 2023;24(4):59–66. DOI: 10.17650/2070-9781-2023-24-4-59-66.

10. Kaltsas A. Oxidative stress and male infertility: the protective role of antioxidants. Medicina (Kaunas). 2023;59(10):1769. DOI: 10.3390/medicina59101769

11. Bisht S., Faiq M., Tolahunase M., Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14(8):470-485. DOI: 10.1038/nrurol.2017.69

12. Ahmad K.A., Yuan Yuan D., Nawaz W., Ze H. et al. Antioxidant therapy for management of oxidative stress induced hypertension. Free Radic Res. 2017;51(4):428-438. DOI: 0.1080/10715762.2017.1322205

13. Agarwal A., Cannarella R., Saleh R. et al. Impact of antioxidant therapy on natural pregnancy outcomes and semen parameters in infertile men: a systematic review and metaanalysis of randomized controlled trials. World J Mens Health. 2023;41(1):14-48. DOI: 10.5534/wjmh.220067

14. Ali M., Martinez M., Parekh N. Are antioxidants a viable treatment option for male infertility? Andrologia. 2021;53(1):e13644. DOI: 10.1111/and.13644

15. Galano A., Tan D.X., Reiter R.J. On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res. 2013;54(3):245-257. DOI: 10.1111/jpi.12010

16. Абсатарова Ю.С., Андреева Е.Н., Шереметьева Е.В., Григорян О.Р. Мелатонин в репродукции человека. Проблемы репродукции. 2016;22(1):8 11. DOI: 10.17116/repro20162218-11.

17. Barlow-Walden L.R., Reiter R.J. et al. Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int. 1995;26(5):497-502. DOI: 10.1016/0197-0186(94)00154-m

18. Rodriguez C., Mayo J.C., Sainz R.M. et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004;36(1):1-9. DOI: 10.1046/j.1600-079x.2003.00092.x

19. Galano A., Medina M.E., Tan D.X., Reiter R.J. Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis. J Pineal Res. 2015;58(1):107-116. DOI: 10.1111/jpi.12196

20. García J.J., López-Pingarrón L., Almeida-Souza P. et al. Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review. J Pineal Res. 2014;56(3):225-237. DOI: 10.1111/jpi.12128

21. Reiter RJ, Tan DX, Kim SJ, Qi W. Melatonin as a pharmacological agent against oxidative damage to lipids and DNA. Proc West Pharmacol Soc. 1998; 41:229-236.

22. Venegas C., García J.A., Escames G. et al. Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res. 2012;52(2):217-227. DOI: 10.1111/j.1600-079X.2011.00931.x

23. Cosme P., Rodríguez A.B., Garrido M., Espino J. Coping with oxidative stress in reproductive pathophysiology and assisted reproduction: melatonin as an emerging therapeutical tool. Antioxidants (Basel). 2022;12(1):86. DOI: 10.3390/antiox12010086

24. Hardeland R. Taxon- and site-specific melatonin catabolism. Molecules. 2017;22(11):2015. DOI: 10.3390/molecules22112015

25. McCubrey J.A., Lahair M.M., Franklin R.A. Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal. 2006;8(9-10):1775-1789. DOI: 10.1089/ars.2006.8.1775

26. Galano A., Tan D.X., Reiter R.J. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res. 2011;51(1):1-16. DOI: 10.1111/j.1600-079X.2011.00916.x

27. Shang X., Ye Z., Yu X., Huang Y. Detection of melatonin in the serum and seminal plasma of fertile and infertile men. Zhonghua Nan Ke Xue. 2004;10(4):293-294.

28. Ortiz A., Espino J., Bejarano I. et al. High endogenous melatonin concentrations enhance sperm quality and shortterm in vitro exposure to melatonin improves aspects of sperm motility. J Pineal Res. 2011;50(2):132-139. DOI: 10.1111/j.1600-079X.2010.00822.x

29. Awad H., Halawa F., Mostafa T., Atta H. Melatonin hormone profile in infertile males. Int J Androl. 2006;29(3):409-413. DOI: 10.1111/j.1365-2605.2005.00624.x

30. Kratz E.M., Piwowar A., Zeman M. et al. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility. Reprod Fertil Dev. 2016; 28(4):507-515. DOI: 10.1071/RD14165

31. H Hassan M., A El-Taieb M. et al. Men with idiopathic oligoasthenoteratozoospermia exhibit lower serum and seminal plasma melatonin levels: Comparative effect of night-light exposure with fertile males. Exp Ther Med;20(1):235-242. DOI: 10.3892/etm.2020.8678

32. Guneli E., Tugyan K., Ozturk H. et al. Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats. Eur Surg Res. 2008;40(4):354-360. DOI: 10.1159/000118032

33. Жук Т.В., Яворская С.Д., Востриков В.В. Ожирение, репродукция и оксидативный стресс. Ожирение и метаболизм. 2017;14(4):16-22. DOI: 10.14341/omet2017416-22

34. Saidi A.O., Akintayo C.O., Atuma C.L. et al. Melatonin supplementation preserves testicular function by attenuating lactate production and oxidative stress in high fat diet-induced obese rat model. Theriogenology. 2022; 187:19-26. DOI: 10.1016/j.theriogenology.2022.02.029

35. Nasiraei-Moghadam S., Parivar K., Ahmadiani A. et al. Food deprivation and social inequality may lead to oxidative damage: a study on the preventive role of melatonin in the male rat reproductive system. Reprod Fertil Dev. 2016; 28:1232-1239. DOI: 10.1071/RD14432

36. Безруков Е.А., Проскура А.В. Взаимосвязь окислительного стресса и повреждения генетического материала сперматозоидов. Проблемы репродукции. 2016; 22(6): 103-109. DOI: 10.17116/repro2016226103-109. Bezrukov EA, Proskura AV. Relation between oxidative stress and sperm DNA damage. Russian Journal of Human Reproduction. 2016; 22(6):103 109. (In Russ.) DOI: 10.17116/repro2016226103-109

37. Dehdari Ebrahimi N., Sadeghi A., Ala M. et al. Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models. Front Endocrinol (Lausanne). 2023; 14:1202560. DOI: 10.3389/fendo.2023.1202560

38. Take G., Erdogan D., Helvacioglu F. et al. Effect of melatonin and time of administration on irradiation-induced damage to rat testes. Braz J Med Biol Res. 2009;42(7):621-628. DOI: 10.1590/s0100-879x2009000700006

39. Hussein M.R., Abu-Dief E.E., Abou El-Ghait A.T. et al. Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats: an animal model. Int J Exp Pathol. 2006;87(3):237-250. DOI: 10.1111/j.1365-2613.2006.00480.x

40. Peng Z., Xin W.Z., Sheng Z.Y. et al. Melatonin alleviates cisplatin-induced mice spermatogenesis defects. Reprod Toxicol. 2023; 119:108391. DOI: 10.1016/j.reprotox.2023.108391

41. Wang Z., Teng Z., Wang Z. et al. Melatonin ameliorates paclitaxel-induced mice spermatogenesis and fertility defects. J Cell Mol Med. 2022;26(4):1219-1228. DOI: 10.1111/jcmm.17177

42. Dehdari Ebrahimi N., Sadeghi A., Shojaei-Zarghani S. et al. Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and metaanalysis of animal studies. Front Endocrinol (Lausanne). 2023; 14:1184745. DOI: 10.3389/fendo.2023.1184745

43. Ji Y.L., Wang H., Meng C. et al. Melatonin alleviates cadmiuminduced cellular stress and germ cell apoptosis in testes. J Pineal Res. 2012;52(1):71-79. DOI: 10.1111/j.1600-079X.2011.00921.x 44. Sobhani M., Rouzbehi A., Mahmoodi R., Sobhani Z. The protective effect of melatonin on sperm morphology and histology of the rat testis damage induced by cadmium chloride. J Mazandaran Univ Med Sci. 2015; 25 (123) :32-44.

44. Bustos-Obregón E., Poblete D., Catriao R., Fernandes F.H. Protective role of melatonin in mouse spermatogenesis induced by sodium arsenite. Int J Morphol Int J Morphol. 2013; 31:849. DOI: 10.4067/S0717-95022013000300012

45. Olayaki L.A., Alagbonsi I.A., Abdulrahim A.H. et al. Melatonin prevents and ameliorates lead-induced gonadotoxicity through antioxidative and hormonal mechanisms. Toxicol Ind Health. 2018; 34(9):596-608. DOI: 10.1177/0748233718773508

46. Dehdari Ebrahimi N., Parsa S., Nozari F. et al. Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies. Front Endocrinol (Lausanne). 2023; 14:1119553. DOI: 10.3389/fendo.2023.1119553

47. Kanter M. Protective effects of melatonin on testicular torsion/detorsion-induced ischemia-reperfusion injury in rats. Exp Mol Pathol. 2010; 89(3):314-320. DOI: 10.1016/j.yexmp.2010.07.006

48. Semercioz A., Onur R., Ogras S., Orhan I. Effects of melatonin on testicular tissue nitric oxide level and antioxidant enzyme activities in experimentally induced left varicocele. Neuro Endocrinol Lett. 2003;24(1-2):86-90.

49. Makris A., Alevra A.I., Exadactylos A., Papadopoulos S. The role of melatonin to ameliorate oxidative stress in sperm cells. Int J Mol Sci. 2023;24(20):15056. DOI: 10.3390/ijms242015056

50. Zhao F., Whiting S., Lambourne S. et al. Melatonin alleviates heat stress-induced oxidative stress and apoptosis in human spermatozoa. Free Radic Biol Med. 2021;164: 410-416. DOI: 10.1016/j.freeradbiomed.2021.01.014

51. Malmir M., Naderi Noreini S., Ghafarizadeh A. et al. Ameliorative effect of melatonin on apoptosis, DNA fragmentation, membrane integrity and lipid peroxidation of spermatozoa in the idiopathic asthenoteratospermic men: In vitro. Andrologia. 2021;53(2):e13944. DOI: 10.1111/and.13944

52. Zhang X.Y., Xiong Y.M., Tan Y.J. et al. Melatonin rescues impaired penetration ability of human spermatozoa induced by mitochondrial dysfunction. Reproduction. 2019;158(5):465-475.DOI: 10.1530/REP-19-0231

53. Monllor F., Espino J., Marchena A.M. et al. Melatonin diminishes oxidative damage in sperm cells, improving assisted reproductive techniques. Turk J Biol. 2017;41(6):881-889. DOI: 10.3906/biy-1704-45

54. Pérez-Torres I., Guarner-Lans V., Rubio-Ruiz M.E. Reductive Stress in inflammation-associated diseases and the pro-oxidant effect of antioxidant agents. Int J Mol Sci. 2017;18(10):2098. DOI: 10.3390/ijms18102098

55. Halliwell B. The antioxidant paradox. Lancet. 2000; 355(9210):1179-1180. DOI: 10.1016/S0140-6736(00)02075-4

56. Lu X.L., Liu J.J., Li J.T. et al. Melatonin therapy adds extra benefit to varicecelectomy in terms of sperm parameters, hormonal profile and total antioxidant capacity: A placebocontrolled, double-blind trial. Andrologia. 2018; 50(6):e13033. DOI: 10.1111/and.13033

57. Bejarano I., Monllor F., Marchena A.M. et al. Exogenous melatonin supplementation prevents oxidative stressevoked DNA damage in human spermatozoa. J Pineal Res. 2014;57(3):333-339. DOI: 10.1111/jpi.12172

Andrology and Genital Surgery. 2024; 25: 15-23

Melatonin and male oxidative stress infertility

Belyi L. E.

https://doi.org/10.62968/2070-9781-2024-25-3-15-23

Abstract

Among couples unable to conceive a child, infertility is explained by the male factor in about 50% of cases. The etiology of male infertility remains uncertain in 30-50% of patients. One of the frequent etiological factors of male infertility is oxidative stress, a status in which an unbalance between the production of reactive oxygen species and the mechanisms of antioxidant protection. Today, the term «male oxidative stress infertility» has been proposed as a new descriptor for infertile men with a combination of abnormal sperm characteristics and oxidative stress. Along with the use of traditional antioxidants, it is necessary to search for new molecules to combat oxidative stress in infertile men. A promising strategy is to use melatonin, a hormone secreted by the pineal gland, as an antioxidant.
The review examines the antioxidant effects of the melatonin metabolic cascade. The results of studies on the relationship between the level of melatonin in seminal plasma and male fertility are presented. New scientific data on the protective potential of melatonin against oxidative stress caused by various metabolic disorders, anticancer chemo- and radiation therapy and other pathogenetic conditions and negative effects are presented. The research on the prospects of using melatonin to protect spermatozoa from oxidative damage in the implementation of assisted reproductive technologies is analyzed. The interim results of studies on the possibility of using melatonin as a dietary supplement in infertile men are summarized.

References

2. Rutstein S.O., Shah I.H. ORC Macro; World Health Organization. Infecundity, infertility, and childlessness in developing countries. Calverton: World Health Organization; 2004.

3. Kumar N., Singh A.K. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015;8(4):191-196. DOI: 10.4103/0974-1208.170370

5. Naumov N.P., Shcheplev P.A., Polozov V.V. Rol' antioksidantov v profilaktike muzhskogo besplodiya. Andrologiya i genital'naya khirurgiya 2019;20(1):22–29. DOI: 10.17650/2070-9781-2019-20-1-22-29.

7. World Health Organization. WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Couple. 2000, Cambridge University Press: Cambridge.

8. Takalani N.B., Monageng E.M., Mohlala K. et al. Role of oxidative stress in male infertility. Reprod Fertil. 2023;4(3):e230024. DOI: 10.1530/RAF-23-0024

9. Gvasaliya B.R., Isaeva A.V., Babaev M.U. Mesto antioksidantov v terapii muzhskogo besplodiya. Andrologiya i genital'naya khirurgiya 2023;24(4):59–66. DOI: 10.17650/2070-9781-2023-24-4-59-66.

10. Kaltsas A. Oxidative stress and male infertility: the protective role of antioxidants. Medicina (Kaunas). 2023;59(10):1769. DOI: 10.3390/medicina59101769

11. Bisht S., Faiq M., Tolahunase M., Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14(8):470-485. DOI: 10.1038/nrurol.2017.69

12. Ahmad K.A., Yuan Yuan D., Nawaz W., Ze H. et al. Antioxidant therapy for management of oxidative stress induced hypertension. Free Radic Res. 2017;51(4):428-438. DOI: 0.1080/10715762.2017.1322205

14. Ali M., Martinez M., Parekh N. Are antioxidants a viable treatment option for male infertility? Andrologia. 2021;53(1):e13644. DOI: 10.1111/and.13644

15. Galano A., Tan D.X., Reiter R.J. On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res. 2013;54(3):245-257. DOI: 10.1111/jpi.12010

16. Absatarova Yu.S., Andreeva E.N., Sheremet'eva E.V., Grigoryan O.R. Melatonin v reproduktsii cheloveka. Problemy reproduktsii. 2016;22(1):8 11. DOI: 10.17116/repro20162218-11.