Study of the effect of CAG polymorphism of the androgen receptor (AR) gene on spermatological parameters in Russian men
https://doi.org/10.25557/2073-7998.2020.10.19-31
Abstract
Polymorphism of CAG repeats in exon 1 of the androgen receptor gene (AR/HUMARA) is associated with pathozoospermia and male sub-/infertility, but its effect on spermatogenesis and seminal fluid parameters is under evaluated. The article presents the results of a study of CAG repeats in AR gene on semen parameters in Russian male patients from infertile couples with pathozoospermia (n = 451), and in normozoospermic men, a control group (n = 131). The analysis of the groups revealed no dependence of the concentration indices, the total amount and amount (%) of progressively motile («PR»), morphologically normal and live spermatozoa from the number of CAG repeats of the AR gene. Teratozoospermic patients have statistically significantly higher number of CAG repeats, than men without teratozoospermia (22.37 ± 3.20 versus 22.15 ± 3.12; p = 0.02).
About the Authors
L. P. Melikyan
Research Centre for Medical Genetics
Russian Federation
Russian Federation
E. A. Bliznetz
Research Centre for Medical Genetics
Russian Federation
Russian Federation
M. I. Shtaut
Research Centre for Medical Genetics
Russian Federation
Russian Federation
A. O. Sedova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
T. M. Sorokina
Research Centre for Medical Genetics
Russian Federation
Russian Federation
L. F. Kurilo
Research Centre for Medical Genetics
Russian Federation
Russian Federation
A. V. Polyakov
Research Centre for Medical Genetics
Russian Federation
Russian Federation
V. B. Chernykh
Research Centre for Medical Genetics
Russian Federation
Russian Federation
References
1. Dabaja A.A., Schlegel P.N. Medical treatment of male infertility. Transl. Androl. Urol. 2014; 3(1): 9-16. doi: 10.3978/j.issn.2223-4683.2014.01.06.
2. Winters B.R., Walsh T.J. The epidemiology of male infertility. Urol. Clin. North. Am. 2014; 41(1): 195-204. doi: 10.1016 / j.ucl.2013.08.006.
3. Smith J.F., Walsh T.J., Shindel A.W. et al. Sexual, marital, and social impact of a man’s perceived infertility diagnosis. J. Sex. Med. 2009; 6(9): 2505-2515. doi: 10.1111/j.1743-6109.2009.01383.x.
4. Batiha O., Haifawi S., Al-Smadi M. et al. Molecular analysis of CAG repeat length of the androgen receptor gene and Y chromosome microdeletions among Jordanian azoospermic infertile males. Andrologia 2018; 50(4): e12979. doi: 10.1111/and.12979.
5. Bain D.L., Heneghan A.F., Connaghan-Jones K.D., Miura M.T. Nuclear receptor structure: implications for function. Annu. Rev. Physiol. 2007; 60: 201-220. doi: 10.1146/annurev.physiol.69.031905. 160308.
6. MacLean H.E., Warne G.L., Zajac J.D. Localization of functional domains in the androgen receptor. J. Steroid. Biochem. Mol. Biol. 1997; 62(4): 233-242. doi: 10.1016/s0960-0760(97)00049-6.
7. Меликян Л.П., Черных В.Б. Полиморфизм CAG-повторов гена андрогенового рецептора, болезнь Кеннеди и мужское бесплодие. Андрология и генитальная хирургия. 2019; 20(2): 35-39.
8. Rajender S., Singh L., Thangaraj K. Phenotypic heterogeneity of mutations in androgen receptor gene. Asian J. Androl. 2007; 9(2): 147-179. doi: 10.1111/j.1745-7262.2007.00250.x.
9. O’Hara L., Smith L.B. Androgen receptor roles in spermatogenesis and infertility. Best Practice & Research Clinical Endocrinology & Metabolism 2015; 29(4): 595-605. doi: 10.1016/j.beem.2015.04.006.
10. Ferlin A., Raicu F., Gatta V. et al. Male infertility: role of genetic background. Reprod. Biomed. Online 2007; 14(6): 734-45. doi: 10.1016/s1472-6483(10)60677-3.
11. Milatiner D., Halle D., Huerta M. et al. Associations between androgen receptor CAG repeat length and sperm morphology. Hum. Reprod 2004; 19(6): 1426-1430. doi: 10.1093/humrep/deh251.
12. Pan B., Li R., Chen Y. et al. Genetic Association Between Androgen Receptor Gene CAG Repeat Length Polymorphism and Male Infertility: A Meta-Analysis. Medicine (Baltimore) 2016; 95(10): e2878. doi: 10.1097/MD.0000000000002878.
13. Giagulli V.A., Carbone M.D., De Pergola G. et al. Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility? J. Assist. Reprod Genet. 2014; 31(6): 689-697. doi: 10.1007/s10815-014-0221-4.
14. Руководство ВОЗ по исследованию и обработке эякулята человека. 5-е изд. М.: Капитал Принт, 2012. 291 с.
15. Щагина О.А., Миронович О.Л., Забненкова В.В. и др. Экспансия CAG-повтора в экзоне 1 гена AR у больных спинальной амиотрофией. Медицинская генетика 2017; 16(9): 31-36.
16. Yong E.L., Loy C.J., Sim K.S. Androgen receptor gene and male infertility. Hum. Reprod Update 2003; 9(1): 1-7. doi: 10.1093/humupd/dmg003.
17. Rajpert-De Meyts E., Leffers H., Petersen J.H. et al. CAG repeat length in androgen-receptor gene and reproductive variables in fertile and infertile men. Lancet 2002; 359(9300): 44-46. doi: 10.1016/s0140-6736(02)07280-x.
18. La Spada A.R., Wilson E.M., Lubahn D.B. et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991; 352(6330): 77-79. doi: 10.1038/352077a0.
19. Chamberlain N.L., Driver E.D., Miesfeld R.L. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994; 22(15): 3181-3186. doi: 10.1093/nar/22.15.3181.
20. Фесай О.А., Кравченко С.А., Тыркус М.Я. и др. CAG-полиморфизм гена андрогенового рецептора у мужчин с азооспермией и олигозооспермией из Украины. Цитология и генетика. 2009; 43(6): 45-51.
21. Меликян Л.П., Близнец Е.А., Поляков А.В. и др. Полиморфизм CAG-повторов в экзоне 1 гена андрогенового рецептора у российских мужчин с нормозооспермией и патозооспермией. Генетика. 2020; 56(8): 1-7.
22. Giovannucci E., Stampfer M.J., Krithivas K. et al. The CAG repeats within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl. Acad. Sci. USA 1997; 94(7): 3320-3323. doi: 10.1073/pnas.94.7.3320.
23. Stanford J.L., Just J.J., Gibbs M. et al. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res. 1997; 57(6): 1194-1198.
24. Hsing A.W., Gao Y.T., Wu G. et al. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res. 2000; 60(18): 5111-5116.
25. Kukuvitis A., Georgiou I., Bouba I. et al. Association of oestrogen receptor α polymorphisms and androgen receptor CAG trinucleotide repeats with male infertility: a study in 109 Greek infertile men. Int. J. Androl. 2002; 25(3): 149-152. doi: 10.1046/j.1365-2605.2002. 00339.x.
26. Wallerand H., Rémy-Martin A., Chabannes E. et al. Relationship between expansion of the CAG repeat in exon 1 of the androgen receptor gene and idiopathic male infertility. Fertil. Steril. 2001; 76(4): 769-774. doi: 10.1016/s0015-0282(01)01987-2.
27. Михайленко Д.С., Бабенко О.В., Никифорова О.К. и др. Молекулярно-генетический анализ области AZF, гена CFTR и CAG-повтора гена AR у мужчин с бесплодием. Проблемы репродукции 2005; (6): 52-55.
28. Nenonen H.A., Giwercman A., Hallengren E. et al. Non-linear association between androgen receptor CAG repeat length and risk of male subfertility a meta-analysis. Int. J. Androl. 2011; 34(4): 327-332. doi: 10.1111/j.1365-2605.2010.01084.x.
29. Lazaros L., Xita N., Kaponis A. et al. Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality. Andrologia 2008; 40(3): 186-91. doi: 10.1111/j.1439-0272.2008.00835.x.
Review
For citations:
Melikyan L.P., Bliznetz E.A., Shtaut M.I., Sedova A.O., Sorokina T.M., Kurilo L.F., Polyakov A.V., Chernykh V.B. Study of the effect of CAG polymorphism of the androgen receptor (AR) gene on spermatological parameters in Russian men. Medical Genetics. 2020;19(10):19-31. (In Russ.) https://doi.org/10.25557/2073-7998.2020.10.19-31
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