Mitochondrial DNA copy number in sperm of hiv-infected men receiving antiretroviral therapy


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Abstract

Objective. To study mitochondrial DNA (mtDNA) content in sperm samples of HIV-infected men receiving antiretroviral therapy (ARVT). Materials and methods. This prospective clinical study included 190patients who presented for the assessment of fertility and achieving conception. The main group consisted of 94 HIV-infected men; the control group included 96 patients without HIV infection. The quantitative assessment of mtDNA deletions (mtDNAdel-), total mtDNA copy number (mtDNAtotal) and their ratio (mtDNAtotal / mtDNAdel-) was carried out in 58 and 96 samples, respectively, using real-time polymerase chain reaction (PCR) method. Results. The median age of HIV-infected men was 37(33; 39) years, duration of the disease was 5 (2; 11) years. The median duration of receiving ARVT was 2 (1; 5) years. The patients of groups were similar in mtDNAdel-(1.9 (0.9; 5.9) and 2.4 (1.9; 5.6); р=0.54), mtDNAtotal (5.4 (3.7; 9.8) and 5.5 (3.5; 8.2); р=0.62) and their ratio mtDNAtotal /mtDNAdel- (2.4(1.5; 3.9) and 1.9 (1.3; 3.0); р=0.09), respectively. In the group with severe sperm abnormality there was a negative correlation between ARVT duration and copy number of mtDNAtotal (r=-0.627; р=0.01), as well as between ARVT duration and mtDNAdel- level (r=-0.542; р=0.04). The pronounced negative correlation was revealed between CD4+ level and ratio mtDNAtotal / mtDNAdel- (r=-0.29; р=0.03). Conclusion. HIV-infected men did not show significant differences in sperm mtDNA copy number in comparison with the men of the control group. HIV-infected men with severe sperm abnormality had inverse relationship between the levels of mtDNAtotal, mtDNAdel- and ARVT duration; mtDNAdel- content was negatively correlated to the immune system state.

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About the authors

S. G Perminova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: perisvet@list.ru
Cand. Med. Sci.; Leading Researcher, Gynecology Department One 4, Oparin St., Moscow 117997

E. V Mityurina

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: mity-elena@yandex.ru
Cand. Med. Sci.; Researcher, Gynecology Department One 4, Oparin St., Moscow 117997

F. N Selimova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: doc.fselimova@mail.ru
Postgraduate Student, Gynecology Department One 4, Oparin St., Moscow 117997

O. A Burmenskaya

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_bourmenskaya@oparina4.ru
BD; Head, Laboratory of Cancer Genetics 4, Oparin St., Moscow 117997

N. V Kozyrina

Central Research Institute of Epidemiology, Federal Service on Customers' Rights Protection and Human Well-being Surveillance

Email: nad-kozyrina@yandex.ru
Cand. Med. Sci., Senior Researcher 3a, Novogireevskaya St., Moscow 111123

A. V Kravchenko

Central Research Institute of Epidemiology, Federal Service on Customers' Rights Protection and Human Well-being Surveillance

Email: alexey-kravtchenko@yandex.ru
MD; Professor, Leading Researcher 3a, Novogireevskaya St., Moscow 111123

References

  1. Федеральный научно-методический центр по профилактике и борьбе со СПИДом ФБУН Центрального НИИ эпидемиологии Роспотребнадзора. Доступно по: http://www.hivrussia.info
  2. Nicopoullos J.D., Almeida P., Vourliotis M., GfUing-Smith C. A decade of the sperm-washing programme: correlation between markers of HIV and seminal parameters. HIV Med. 2011; 12(4): 195-201. https://dx.doi.org/10.1111/j.1468-1293.2010.00868.x.
  3. Kehl S., Weigel M., Muller D., Gentili M., Hornemann A., SUtterlin M. HIV-1 infection and modern antiretroviral therapy impair sperm quality. Arch. Gynecol. Obstet. 2011; 284(1): 229-33. https://dx.doi.org/10.1007/s00404-011-1898-6.
  4. Bujan L., Sergerie M., Moinard N., Martinet S., Porte L., Massip P. et al. Decreased semen volume and spermatozoa motility in HIV-1-infected patients under antiretroviral treatment. J. Androl. 2007; 28(3): 444-52. https://dx.doi. org/10.2164/jandrol.106.001529.
  5. Lewis W., Dalakas M.C. Mitochondrial toxicity of antiviral drugs. Nat. Med. 1995; 1(5): 417-22. https://dx.doi.org/10.1038/nm0595-417.
  6. Michaels G.S., Hauswirth W.W., Laipis P.J. Mitochondrial DNA copy number in bovine oocytes and somatic cells. Dev. Biol. 1982; 94(1): 246-51. https://dx.doi. org/10.1016/0012-1606(82)90088-4.
  7. Ramalho-Santos J., Varum S., Amaral S., Mota P.C., Sousa A.P., Amaral A. Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells. Hum. Reprod. 2009; 15(5): 553-72. https://dx.doi. org/10.1093/humupd/dmp016.
  8. Pelliccione F., Micillo A., Cordeschi G., D’Angeli A., Necozione S., Gandini L. et al. Altered ultrastructure of mitochondrial membranes is strongly associated with unexplained asthenozoospermia. Fertil. Steril. 2011; 95(2): 641-6. https://dx.doi. org/0.1016/j.fertnstert.2010.07.1086.
  9. Hulgan T., Morrow J., D’Aquila R.T., Raffanti S., Morgan M., Rebeiro P., Haas D.W. Oxidant stress is increased during treatment of human immunodeficiency virus infection. Clin. Infect. Dis. 2003; 37(1): 1711-7. https:// dx.doi.org/10.1086/379776.
  10. Aitken R.J., Koppers A.J. Apoptosis and DNA damage in human spermatozoa. Asian J. Androl. 2011; 13(1): 36-42. https://dx.doi.o/10.1038/aja.2010.68.
  11. Blumer C.G., Restelli A.E., Giudice P.T., Soler T.B., Fraietta R., Nichi M. et al. Effect of varicocele on perm function and semen oxidative stress. BJU Int. 2012; 109(2): 259-65. https://dx.doi.org/10.1111/j.1464-410X.2011.10240.x.
  12. Божедомов В.А., Торопцева М.В., Ушакова И.В., Спориш Е.А., Ловыгина Н.А., Липатова Н.А. Активные формы кислорода и репродуктивная функция мужчин: фундаментальные и клинические аспекты (обзор литературы). Андрология и генитальная хирургия. 2011; 12(3): 15-21
  13. Van Leewen L., Repping S., de Baar M.P., Wit F.W., Prins J.M., van der Veen F., Reiss P. Ch.6: Increase of spermatozoal mtDNA copy numbers during first twelve weeks of first-line HAART. In: van Leeuwen E. Male reproduction and HIV-1 infection. 2009: 75-86.
  14. ВОЗ, Медико-генетический научный центр Российской академии медицинских наук. Руководство ВОЗ по исследованию и обработке эякулята человека. Пер. с англ. 5-е изд. Курило Л.Ф., ред. М.: Издательство «КАПИТАЛ ПРИНТ»; 2012.
  15. Van Leeuwen E., Cornelissen M., de Vries J.W., Lowe S.H., Jurriaans S., Repping S, van der Veen F. Semen parameters of a semen donor before and after infection with human immunodeficiency virus type 1: case report. Hum. Reprod. 2004; 19(12): 2845-8. https://dx.doi.org/10.1093/humrep/deh510.
  16. Van Leeuwen E., Wit F.W., Prins J.M., Reiss P., van der Veen F., Repping S. Semen quality remains stable during 96 weeks of untreated human immunodeficiency virus-1 infection. Fertil. Steril. 2008; 90(3): 636-41. https://dx.doi.org/10.1016/j. fertnstert.2007.06.102.
  17. Drobnis E, Nangia K. Antivirals and male reproduction Adv. Exp. Med. Biol. 2017; 1034: 163-8. https://dx.doi.org/10.1007/978-3-319-69535-8_11.
  18. Muller C.H., Coombs R.W., Krieger J.N. Effects of clinical stage and immunological status on semen analysis results in human immunodeficiency virus type 1-seropositive men. Andrologia. 1998; 30(Suppl. 1): 15-22. https:// dx.doi.org/10.1111/j.1439-0272.1998.tb02821.x.
  19. Dondero F, Rossi T., D’Offizi G., Mazzilli F., Rosso R., Sarandrea N. et al. Semen analysis in HIV seropositive men and in subjects at high risk for HIV infection. Hum. Reprod.1996; 11(4): 765-8. https://dx.doi.org/10.1093/oxfordjournals. humrep.a019251.
  20. Dulioust E., Du A.L., Costagliola D., Guibert J., Kunstmann J.M., Heard I. et al. Semen alterations in HIV-1-infected men. Hum. Reprod. 2002; 17(8): 2112-8. https://dx.doi.org/10.1093/humrep/17.8.2112.
  21. Wu H., Huffman A.M., Whitcomb B.W., Josyula S., Labrie S., Tougias E. et al. Sperm mitochondrial DNA measures and semen parameters among men undergoing fertility treatment. Reprod. Biomed. Online. 2019; 38(1): 66-75. https://dx.doi.org/10.1016/j.rbmo.2018.10.004.
  22. Kao S.H., Chao H.T., Wei Y.H. Multiple deletions of mitochondrial DNA are associated with the decline of motility and fertility of human spermatozoa. Mol. Hum. Reprod. 1998; 4(7): 657-66. https://dx.doi.org/10.1093/molehr/4.7.657.
  23. Lee H.C., Yin P.H., Lu C.Y., Chi C.W., Wei Y.H. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem J. 2000; 348(Pt 2): 425-32.
  24. Maisonneuve C., Igoudjil A., Begriche K., Letteron P., Guimont M.C., Bastin J. et al. Effects of zidovudine, stavudine and beta-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting. Antivir. Ther. 2004; 9(5): 801-10.
  25. Diehl S., Vernazza P., Trein A., Schnaitmann E., Grimbacher B., Setzer B. et al. Mitochondrial DNA and sperm quality in patients under antiretroviral therapy. AIDS. 2003; 17(3): 450-1. https://dx.doi.org/10.1097/00002030-200302140-00025.
  26. White D.J., Mital D., Taylor S., St John J.C. Sperm mitochondrial DNA deletions as a consequence of long term highly active antiretroviral therapy. AIDS. 2001; 15(8): 1061-2. https://dx.doi.org/10.1097/00002030-200105250-00017.

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