Сперматозоидтар ДНҚ фрагментациясы дамуындағы клиникалық факторлардың, өмір салты мен қоршаған ортаның рөлі

Сперматозоидтар ДНҚ фрагментациясы – эякуляттың стандартты зерттеуін толықтыратын және гаметалардың генетикалық материалының зақымдануын көрсететін ерлер фертильділігінің маңызды функционалдық көрсеткіші.

Шолудың мақсаты – сперматозоидтар ДНҚ фрагментациясының жоғарылауымен байланысты биологиялық, клиникалық, мінез-құлықтық және қоршаған орта факторлары жөніндегі заманауи деректерді жүйелеу. PubMed, Scopus және Web of Science базаларындағы кәсіби ұсынымдар, жүйелі шолулар, мета-талдаулар және негізгі түпнұсқалық зерттеулер талданды. Хроматин ремоделденуінің бұзылыстары, тотығу стрессі, апоптоз, сперматозоидтардың жетілу ақаулары, сондай-ақ жас, варикоцеле, қабыну, инфекциялар, метаболизмдік бұзылыстар, онкологиялық аурулар, қызба, темекі шегу, алкоголь, семіздік, дене белсенділігі, жыныстық қатынастан тежелу, жылу әсері және қоршаған орта ластағыштарының ықпалы қарастырылды.

Ең тұрақты байланыстар варикоцеле, айқын тотығу стрессі, темекі шегу, жас ұлғаюы және кейбір уытты әсерлер үшін анықталды. Клиникалық интерпретацияда талдау әдісі, пациент анамнезі және өзгертілетін қауіп факторлары ескерілуі тиіс.

1. Agarwal A., Baskaran S., Parekh N., Cho C.L., Henkel R., Vij S. et al. Male infertility. Lancet. 2021; 397 (10271): 319-333. https://doi.org/10.1016/S0140-6736(20)32667-2

2. Lamb D.J. Is male infertility an early warning of more serious diseases? Endocrinology. 2026; 167 (4): bqaf187. https://doi.org/10.1210/endocr/bqaf187

3. Pinggera G.M., Sengupta P., Mostafa T., Bahar F., Calogero A.E., Srinivasan S. et al. Reassessing semen analysis: clinical insights beyond sperm count and motility. Reprod. Med. Biol. 2026; 25 (1): e70096. https://doi.org/10.1002/rmb2.70096

4. Björndahl L., Kirkman Brown J., other Editorial Board Members of the WHO Laboratory Manual for the Examination and Processing of Human Semen. The sixth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: ensuring quality and standardization in basic examination of human ejaculates. Fertil. Steril. 2022; 117 (2): 246-251. https://doi.org/10.1016/j.fertnstert.2021.12.012

5. Agarwal A., Majzoub A., Baskaran S., Panner Selvam M.K., Cho C.L., Henkel R. et al. Sperm DNA fragmentation: a new guideline for clinicians. World J. Mens Health. 2020; 38 (4): 412-471. https://doi.org/10.5534/wjmh.200128

6. Yifu P., Lei Y., Shaoming L., Yujin G., Xingwang Z. Sperm DNA fragmentation index with unexplained recurrent spontaneous abortion: a systematic review and meta-analysis. J. Gynecol. Obstet. Hum. Reprod. 2020; 49: 101740. https://doi.org/10.1016/j.jogoh.2020.101740

7. Santi D., Spaggiari G., Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management: meta-analyses. Reprod. Biomed. Online. 2018; 37 (3): 315-326. https://doi.org/10.1016/j.rbmo.2018.06.023

8. Firouzabadi A.M., Fesahat F., Seifati S.M. Dynamic architecture of mammalian paternal chromatin: histone-to-protamine exchange and postfertilization reprogramming. Epigenetics Chromatin. 2025; 18 (1): 83. https://doi.org/10.1186/s13072-025-00651-0

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

10. Rashki Ghaleno L., Alizadeh A., Drevet J.R., Shahverdi A., Valojerdi M. R. Oxidation of sperm DNA and male infertility. Antioxidants. 2021; 10 (1): 97. https://doi.org/10.3390/antiox10010097

11. Moritz L., Hammoud S.S. The art of packaging the sperm genome: molecular and structural basis of the histone-to-protamine exchange. Front. Endocrinol. 2022; 13: 895502. https://doi.org/10.3389/fendo.2022.895502

12. Torres-Flores U., Hernández-Hernández A. The interplay between replacement and retention of histones in the sperm genome. Front. Genet. 2020; 11: 780. https://doi.org/10.3389/fgene.2020.00780

13. Dutta S., Sengupta P., Slama P., Roychoudhury S. Oxidative stress, testicular inflammatory pathways, and male reproduction. Int. J. Mol. Sci. 2021; 22 (18): 10043. https://doi.org/10.3390/ijms221810043

14. Wood G.J.A., Cardoso J.P.G., Paluello D.V., Nunes T.F., Cocuzza M. Varicocele-associated infertility and the role of oxidative stress on sperm DNA fragmentation. Front. Reprod. Health. 2021; 3: 695992. https://doi.org/10.3389/frph.2021.695992

15. Barbagallo F., Cannarella R., Crafa A., Manna C., La Vignera S., Condorelli R. A. et al. The impact of a very short abstinence period on conventional sperm parameters and sperm DNA fragmentation: a systematic review and metaanalysis. J. Clin. Med. 2022; 11 (24): 7303. https://doi.org/10.3390/jcm11247303

16. Lira Neto F.T., Roque M., Esteves S.C. Effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation rates in infertile men with clinical varicocele: a systematic review and meta-analysis. Fertil. Steril. 2021; 116(3): 696-712. https://doi.org/10.1016/j.fertnstert.2021.04.003

17. Agarwal A., Majzoub A., Esteves S.C., Ko E., Ramasamy R., Zini A. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl. Androl. Urol. 2016; 5 (6): 935-950. https://doi.org/10.21037/tau.2016.10.03

18. Schneider S., Balbach M., Jikeli J.F., Fietz D., Nettersheim D., Jostes S. et al. Re-visiting the Protamine-2 locus: deletion, but not haploinsufficiency, renders male mice infertile. Sci. Rep. 2016; 6: 36764. https://doi.org/10.1038/srep36764

19. Shi W.H., Ye M.J., Qin N.X., Zhou Z.Y., Zhou X.Y., Xu N.X. et al. Associations of sperm mtDNA copy number, DNA fragmentation index, and reactive oxygen species with clinical outcomes in ART treatments. Front. Endocrinol. 2022; 13: 849534. https://doi.org/10.3389/fendo.2022.849534

20. Irigoyen P., Mansilla S., Castro L., Cassina A., Sapiro R. Mitochondrial function and reactive oxygen species production during human sperm capacitation: unraveling key players. FASEB J. 2024; 38( 4): e23486. https://doi.org/10.1096/fj.202301957RR

21. Wu S., Yan M., Ge R., Cheng C.Y. Crosstalk between Sertoli and germ cells in male fertility. Trends Mol. Med. 2020; 26 (2): 215-231. https://doi.org/10.1016/j.molmed.2019.09.006

22. Delessard M., Saulnier J., Rives A., Dumont L., Rondanino C., Rives N. Exposure to chemotherapy during childhood or adulthood and consequences on spermatogenesis and male fertility. Int. J. Mol. Sci. 2020; 21 (4): 1454. https://doi.org/10.3390/ijms21041454

23. Chen H., Alves M.B.R., Belleannée C. Contribution of epididymal epithelial cell functions to sperm epigenetic changes and the health of progeny. Hum. Reprod. Update. 2022; 28 (1): 51-66. https://doi.org/10.1093/humupd/dmab029

24. Eldamnhoury E.M., Elatrash G.A., Rashwan H.M., El-Sakka A.I. Association between leukocytospermia and semen interleukin-6 and tumor necrosis factor-alpha in infertile men. Andrology. 2018; 6 (5): 775-780. https://doi.org/10.1111/andr.12513

25. Gonzalez D.C., Ory J., Blachman-Braun R., Nackeeran S., Best J.C., Ramasamy R. Advanced paternal age and sperm DNA fragmentation: a systematic review. World J. Mens Health. 2022; 40 (1): 104-115. https://doi.org/10.5534/wjmh.200195

26. Szabó A., Váncsa S., Hegyi P., Váradi A., Forintos A., Filipov T. et al. Lifestyle-, environmental-, and additional health factors associated with increased sperm DNA fragmentation: a systematic review and meta-analysis. Reprod. Biol. Endocrinol. 2023; 21 (1): 5. https://doi.org/10.1186/s12958-023-01054-0

27. Birowo P., Rahendra Wijaya J., Atmoko W., Rasyid N. The effects of varicocelectomy on the DNA fragmentation index and other sperm parameters: a meta-analysis. Basic Clin. Androl. 2020; 30: 15. https://doi.org/10.1186/s12610-020-00112-6

28. Zhong O., Ji L., Wang J., Lei X., Huang H. Association of diabetes and obesity with sperm parameters and testosterone levels: a meta-analysis. Diabetol. Metab. Syndr. 2021; 13 (1): 109. https://doi.org/10.1186/s13098-021-00728-2

29. Campbell J.M., Lane M., Owens J.A., Bakos H.W. Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis. Reprod. Biomed. Online. 2015; 31 (5): 593-604. https://doi.org/10.1016/j.rbmo.2015.07.012

30. Oktay K., Harvey B.E., Partridge A.H., Quinn G.P., Reinecke J., Taylor H. S. et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J. Clin. Oncol. 2018; 36 (19): 1994-2001. https://doi.org/10.1200/JCO.2018.78.1914

31. Houston B.J., Nixon B., Martin J.H., De Iuliis G.N., Trigg N.A., Bromfield E.G. et al. Heat exposure induces oxidative stress and DNA damage in the male germ line. Biol. Reprod. 2018; 98 (4): 593-606. https://doi.org/10.1093/biolre/ioy009

32. Berg E., Houska P., Nesheim N., Schuppe H.C., Pilatz A., Fijak M. et al. Chronic prostatitis/ chronic pelvic pain syndrome leads to impaired semen parameters, increased sperm DNA fragmentation and unfavorable changes of sperm protamine mRNA ratio. Int. J. Mol. Sci. 2021; 22 (15): 7854. https://doi.org/10.3390/ijms22157854

33. Moreno-Sepulveda J., Rajmil O. Seminal human papillomavirus infection and reproduction: a systematic review and meta-analysis. Andrology. 2021; 9 (2): 478-502. https://doi.org/10.1111/andr.12948

34. Bazzar B., Reshadfar E., Namdar P., Pourbagher D., Bakhtiari Lafmejani R., Soleimanzadeh A. The relationship between seminal microbiome and male reproductive wellness: a systematic review. Biol. Reprod. 2026; 114 (4): 1151-1167. https://doi.org/10.1093/biolre/ioag003

35. Osadchuk L., Kleshchev M., Osadchuk A. Effects of cigarette smoking on semen quality, reproductive hormone levels, metabolic profile, zinc and sperm DNA fragmentation in men: results from a population-based study. Front. Endocrinol. 2023; 14: 1255304. https://doi.org/10.3389/fendo.2023.1255304

36. Mostafa R.M., Nasrallah Y.S., Hassan M.M., Farrag A.F., Majzoub A., Agarwal A. The effect of cigarette smoking on human seminal parameters, sperm chromatin structure and condensation. Andrologia. 2018; 50 (3): e12910. https://doi.org/10.1111/and.12910

37. Axelsson J., Lindh C.H., Giwercman A. Exposure to polycyclic aromatic hydrocarbons and nicotine, and associations with sperm DNA fragmentation. Andrology. 2022; 10 (4): 740-748. https://doi.org/10.1111/andr.13170

38. Trautman A., Gurumoorthy A., Hansen K.A. Effects of alcohol use on sperm chromatin structure: a retrospective analysis. Basic Clin. Androl. 2023; 33(1): 14. https://doi.org/10.1186/s12610-023-00189-9

39. Amor H., Ismaeil A., Jankowski P.M., Smadi M.A.A., Zoubi M.S.A., Juhasz-Böss I. et al. Effects of marijuana and tobacco on male fertility and their relationship to genetic variation of mitochondrial cytochrome C oxidase genes. Sci. Rep. 2025; 15 (1): 7547. https://doi.org/10.1038/s41598-025-91894-0

40. Murphy S.K., Itchon-Ramos N., Visco Z., Huang Z., Grenier C., Schrott R. et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018; 13 (12): 1208-1221. https://doi.org/10.1080/15592294.2018.1554521

41. Nazmara Z., Shirinbayan P., Reza Asgari H., Ahadi R., Asgari F., Maki C. B. et al. The epigenetic alterations of human sperm cells caused by heroin use disorder. Andrologia. 2021; 53 (1): e13799. https://doi.org/10.1111/and.13799

42. Rodrigues A.C.M.A., Gomes M.L.M., Dias F.C.R. Impact of psychostimulant exposure on male fertility and spermatogenic function. Andrology. 2026; 1: 1-14. https://doi.org/10.1111/andr.70312

43. Hashimi M.A., Pinggera G.M., Shah R., Agarwal A. Clinician’s guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids. Asian J. Androl. 2025; 27 (3): 330-341. https://doi.org/10.4103/aja2024104

44. Ganji M., Eslamian G., Amirjannati N., Noormohammadi M., Amirjannati N. Dietary patterns and sperm DNA fragmentation in idiopathic infertile men: a case-control study. Sci. Rep. 2026; 16 (1): 5982. https://doi.org/10.1038/s41598-026-35928-1

45. Michaelsen M.P., Poulsen M., Bjerregaard A.A., Borgstrøm M., Poulsen L. K., Chortsen M.B. et al. The effect of dietary supplements on male infertility in terms of pregnancy, live birth, and sperm parameters: a systematic review and metaanalysis. Nutrients. 2025; 17 (10): 1710. https://doi.org/10.3390/nu17101710

46. Maleki B.H., Tartibian B. High-intensity exercise training for improving reproductive function in infertile patients: a randomized controlled trial. J. Obstet. Gynaecol. Can. 2017; 39 (7): 545-558. https://doi.org/10.1016/j.jogc.2017.03.097

47. Aerts A., Temmerman A., Vanhie A., Vanderschueren D., Antonio L. The effect of endurance exercise on semen quality in male athletes: a systematic review. Sports Med. Open. 2024; 10 (1): 72. https://doi.org/10.1186/s40798-024-00739-z

48. Wang X., Chen Q., Zou P., Liu T., Mo M., Yang H. et al. Sleep duration is associated with sperm chromatin integrity among young men in Chongqing, China. J. Sleep Res. 2018; 27(4): e12615. https://doi.org/10.1111/jsr.12615

49. Wang W., Qikai W., Zilin W., Junyan S., Xiaocui J., Qi L. et al. Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK-PDC axis. Reprod. Biol. Endocrinol. 2025; 23 (1): 127. https://doi.org/10.1186/s12958-025-01458-0

50. Jebli L., Gallissian S., Barèges R., Fournier F., Metzler-Guillemain C., Prades S. et al. The impact of common medications on male fertility: an updated systematic review. Andrology. 2026; 1: 1-52. https://doi.org/10.1111/andr.70381

51. Naelitz B.D., Momtazi-Mar L., Vallabhaneni S., Cannarella R., Vij S.C., Parekh N. V. et al. Testosterone replacement therapy and spermatogenesis in reproductive age men. Nat. Rev. Urol. 2025; 22 (10): 703-719. https://doi.org/10.1038/s41585-025-01032-8

52. Esteves S.C., Zini A., Coward R.M., Evenson D.P., Gosálvez J., Lewis S. E.M. et al. Sperm DNA fragmentation testing: summary evidence and clinical practice recommendations. Andrologia. 2021; 53 (2): e13874. https://doi.org/10.1111/and.13874

53. WHO laboratory manual for the examination and processing of human semen. https://www.who.int/publications/i/item/9789240030787

54. Schlegel P.N., Sigman M., Collura B., De Jonge C.J., Eisenberg M.L., Lamb D.J. et al. Diagnosis and treatment of infertility in men: AUA/ ASRM guideline part I. Fertil. Steril. 2021; 115 (1): 54-61. https://doi.org/10.1016/j.fertnstert.2020.11.015

55. Minhas S., Bettocchi C., Boeri L., Capogrosso P., Carvalho J., Cilesiz N. C. et al. European Association of Urology guidelines on male sexual and reproductive health: 2021 update on male infertility. Eur. Urol. 2021; 80 (5): 603-620. https://doi.org/10.1016/j.eururo.2021.08.014