Андрология и генитальная хирургия. 2012; 13: 45-53
Этиопатогенез аутоиммунных реакций против сперматозоидов
https://doi.org/10.17650/2070-9781-2012-4-45-53Аннотация
Одной из причин мужского бесплодия являются аутоиммунные реакции против сперматозоидов, которые сопровождаются выработкой антиспермальных антител (АСАТ).
Цель исследования – уточнить роль различных факторов (за исключением обструкции) в этиологии иммунного мужского бесплодия.
Материал и методы исследования. Клинико-лабораторное обследование 536 мужчин из бесплодных пар (возраст 18–45 лет); контрольную группу составили фертильные мужчины, жены которых были беременны на сроке 8–16 нед (n = 82). Исследование спермы проводили в соответствии с требованиями ВОЗ. Определение АСАТ в сперме – MAR-тест. Оценку оксидативного стресса выполняли методом люминолзависимой хемилюминесценции. Повреждение хромосом – по фрагментации ДНК методом дисперсии хроматина в геле инертной агарозы с визуальной оценкой под микроскопом образования ореола после кислотной денатурации ДНК и лизирования протеинов ядра. Содержание интерферонов (ИФН) в крови, естественную и индуцированную in vitro продукцию ИФН – по методу Кемпбелла. Диагностику инфекций репродуктивного тракта – методом ПЦР.
Результаты. Существует высоко значимая корреляция между количеством АСАТ с одной стороны и перенесенным орхитом и субклинической травмой яичка с другой. Корреляция варикоцеле – АСАТ отсутствует, но при варикоцеле повышается риск иммунного бесплодия и орхита после травмы; варикоцелэктомия способствует снижению АСАТ при большей степени варикоцеле и менее выраженном аутоиммунном процессе. АСАТ наблюдаются на фоне хламидийной инфекции при повышенной продукции ИФН γ. Крипторхизм и орхипексия, паротит, эпидидимит, грыжесечение, хронический бактериальный простатит и другие потенциальные факторы риска снижения фертильности мужчин не оказали значимого влияния на отношение шансов развития иммунного бесплодия. В большинстве случаев (41 %) иммунное бесплодие кажется идиопатическим, но сопровождается гиперпродукцией активных форм кислорода и повреждением (фрагментацией) ДНК.
Заключение. Иммунное мужское бесплодие полиэтиологично: повреждение гемато-тестикулярного барьера, перекрестные реакции с микроорганизмами, иммунопатологические реакции. Аутоиммунные реакции против сперматозоидов могут рассматриваться как в качестве причины, так и следствия плохого качества спермы, обусловленного генетическими и разными эндо и экзогенными факторами.
Список литературы
1. WHO manual for the standardized investigation and diagnosis of the infertile couple. WHO, 3th ed.: Cambridge university press, 2000. P. 32.
2. Walsh T.J., Turek P.J. Immunologic infertility. In.: Infertility in the male. 4th edition Eds. L.I. Lipshuitz,
3. S.S. Howards, C.S. Niederberger. Cambridge University Press, 2009. P. 277–94.
4. Francavilla F., Barbonetti A. Male autoimmune infertility. In.: Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 145–153.
5. Божедомов В.А., Лоран О.Б., Сухих Г.Т. Этиология и патогенез мужского аутоиммунного бесплодия. Часть 1 и 2. Андрол и генит хир 2001;1:72–7, 78–87.
6. Krause W.K.H. Sperm function influenced by immune reaction. In.: Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 49–65.
7. Naz R.K. Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 2011;66(1):5–12.
8. Божедомов В.А., Теодорович О.В. Эпидемиология и причины аутоиммунного мужского бесплодия. Урология 2005;1:35–44.
9. Mazumdar M.D., Levine A.S. Antisperm antibodies: etiology, pathogenesis, diagnosis and treatment. Fertil Steril 1998;70:799–810.
10. Kurpisz M., Havryluk A., Nakonechnyj A. et al. Cryptorchidism and long-term consequences. Reprod Biol
11. ;10(1):19–35.
12. Veräjänkorva E., Laato M., Pöllänen P. Analysis of 508 infertile male patients in south-western Finland in 1980–2000: hormonal status and factors predisposing to immunological infertility. Eur J Obstet Gynecol Reprod Biol 2003;111(2):173–8.
13. Al-Daghistani H.I., Hamad A.W., Abdel-Dayem M. et al. Evaluation of serum testosterone, progesterone, seminal antisperm antibody, and fructose levels among Jordanian males with a history
14. of infertility. Biochem Res Int 2010;10:409.
15. Marconi M., Pilatz A., Wagenlehner F. et al. Are antisperm antibodies really associated with proven chronic inflammatory and infectious diseases of the male reproductive tract? Eur Urol 2009;56(4):708–15.
16. Hoover P., Naz R.K. Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma? Int J Androl 2012 Aug;35(4):608–15.
17. Mirilas P., Panayiotides I., Mentessidou A. et al. Effect of testis nondescent or orchidopexy on antisperm antibodies and testis histology in rats. Fertil Steril 2010;94(4):1504–9.
18. Marconi M., Weidner W. Site and risk factors of antisperm antibodies production in the male population. Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 97–109.
19. WHO laboratory manual for the examination and processing of human semen. Fifth ed., WHO, 2010. 271 p.
20. Andrology: male reproductive health and disfunction. 3rd edition. Eds. E. Nieschlag, H.M. Behre, S. Nieschlag. Springer, 2010. Р. 148.
21. Lee R., Goldstein M., Ullery B.W. et al. Experts’ comments: value of serum antisperm antibodies in diagnosing obstructive azoospermia. J Urol 2009;181:264–9.
22. Leonhartsberger N., Gozzi C., Akkad T. et al. Organ-sparing surgery does not lead to greater antisperm antibody levels than orchidectomy. BJU Int 2007;100:371–4.
23. Ozturk U., Ozdemir E., Dede O. et al. Assessment of anti-sperm antibodies in couples after testicular sperm extraction. Clin Invest Med 2011 Jun;34(3):E179–83.
24. Мейл Д., Бростофф Дж., Рот Д.Б., Ройт А. Иммунология, 7-е издание. М., 2007. C. 236, 352–363.
25. Prabha V., Chaudhary N., Kaur S. Molecular mimicry between spermatozoa and bacteria. J Urol 2011 Dec;186(6):2442–7.
26. Jeremias J., Witkin S.S. Molecular approaches to the diagnosis of male infertility. Mol Hum Reprod 1996;2(3):195–202.
27. Божедомов В.А., Николаева М.А. Голубева Е.Л. и др. Аутоиммунные реакции против сперматозоидов: эпидемиология, этиопатогенез, диагностика, лечение. Мужское здоровье и долголетие. 9-я Международная медицинская выставка, 16–17 февраля 2011 г., Москва. Материалы форума, 2011. С. 20–21.
28. Aitken R.J., Clarkson J.S., Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod 1989;41:183–97.
29. Zorn B., Vidmar G., Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm
30. injection. Int J Androl 2003;26:279–85.
31. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 2008;14(3):243–58.
32. Божедомов В.А., Громенко Д.С., Ушакова И.В. и др. Причины оксидативного стресса сперматозоидов. Проблемы репродукции 2008;6:67–73.
33. Nikolaeva M.A., Kulakov V.I., Korotkova I. et al. Antisperm antibodies detection by flow cytometry is affectid by aggregation of antigen-antibody complexes on the surfase of spermatozoa. Hum Reprod
34. ;15:2545–53.
35. Божедомов В.А., Николаева М.А., Ушакова И.В. и др. Роль процессов свободно-радикального окисления в патогенезе мужского иммунного бесплодия. Андрол и генит хир 2010;4:62–6.
36. Zini A., Fahmy N., Belzile E. et al. Antisperm antibodies are not associated with pregnancy rates after
37. IVF and ICSI: systematic review and meta-analysis. Hum Reprod 2011 Jun;26(6):1288–95.
Andrology and Genital Surgery. 2012; 13: 45-53
Etiopathogenesis of autoimmune responses against sperm
https://doi.org/10.17650/2070-9781-2012-4-45-53Abstract
The autoimmune reactions against sperm, which are accompanied by the elaboration of antisperm antibodies (AsAb), are one of the causes of male infertility.
Objective: to specify the role of different factors (other than obstruction) in the etiology of male immune infertility.
Subjects and methods. Clinical and laboratory studies were made in 536 males from infertile couples (their age 18–45 years); a control group comprised fertile men whose wives were 8–16 weeks pregnant (n = 82). Their sperms were examined in accordance with the WHO recommendations. AsAbs in the sperm were determined by a MAR test. Oxidative stress was estimated using luminol-dependent chemiluminescence. Chromosome damage was identified from DNA fragmentation by chromatin dispersion in an inert agarose gel, by making a microscopic examination of halo formation after acid DNA denaturation and nuclear protein lysis. The blood levels of interferons (IFN) and their natural and in vitro induced production were determined by the Campbell method. Reproductive tract infections were diagnosed by polymerase chain reaction.
Results. There is a high significant correlation between the quantity of AsAb, on the one hand, and previous orchitis, as well as subclinical testicular injury, on the other hand. There was no correlation between varicocele and AsAb, but in the former, the risk of immune infertility and orchitis increases after injury; varicocelectomy promotes a reduction in AsAb with the higher degree of varicocele and a less marked autoimmune process. AsAbs are observed during Chlamydia infection with the increased production of IFN-γ. Cryptorchidism and orchiopexy, parotitis, epididymitis, herniotomy, chronic bacterial prostatitis, and other potential risk factors for decreased male fertility had no significant impacts on an odds ratio for developing immune infertility. In the majority (41 %) of cases, immune infertility seems to be idiopathic, but it is accompanied by the hyperproduction of reactive oxygen species and DNA damage (fragmentation).
Conclusion. Male immune infertility is multietiological: blood-testis barrier damage, cross reactions with microorganisms, and immunopathological reactions. Autoimmune reactions against sperm can be considered to be both a cause and a sequence of the bad semen quality caused by genetic and different endo- and exogenous factors.
References
1. WHO manual for the standardized investigation and diagnosis of the infertile couple. WHO, 3th ed.: Cambridge university press, 2000. P. 32.
2. Walsh T.J., Turek P.J. Immunologic infertility. In.: Infertility in the male. 4th edition Eds. L.I. Lipshuitz,
3. S.S. Howards, C.S. Niederberger. Cambridge University Press, 2009. P. 277–94.
4. Francavilla F., Barbonetti A. Male autoimmune infertility. In.: Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 145–153.
5. Bozhedomov V.A., Loran O.B., Sukhikh G.T. Etiologiya i patogenez muzhskogo autoimmunnogo besplodiya. Chast' 1 i 2. Androl i genit khir 2001;1:72–7, 78–87.
6. Krause W.K.H. Sperm function influenced by immune reaction. In.: Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 49–65.
7. Naz R.K. Antisperm contraceptive vaccines: where we are and where we are going? Am J Reprod Immunol 2011;66(1):5–12.
8. Bozhedomov V.A., Teodorovich O.V. Epidemiologiya i prichiny autoimmunnogo muzhskogo besplodiya. Urologiya 2005;1:35–44.
9. Mazumdar M.D., Levine A.S. Antisperm antibodies: etiology, pathogenesis, diagnosis and treatment. Fertil Steril 1998;70:799–810.
10. Kurpisz M., Havryluk A., Nakonechnyj A. et al. Cryptorchidism and long-term consequences. Reprod Biol
11. ;10(1):19–35.
12. Veräjänkorva E., Laato M., Pöllänen P. Analysis of 508 infertile male patients in south-western Finland in 1980–2000: hormonal status and factors predisposing to immunological infertility. Eur J Obstet Gynecol Reprod Biol 2003;111(2):173–8.
13. Al-Daghistani H.I., Hamad A.W., Abdel-Dayem M. et al. Evaluation of serum testosterone, progesterone, seminal antisperm antibody, and fructose levels among Jordanian males with a history
14. of infertility. Biochem Res Int 2010;10:409.
15. Marconi M., Pilatz A., Wagenlehner F. et al. Are antisperm antibodies really associated with proven chronic inflammatory and infectious diseases of the male reproductive tract? Eur Urol 2009;56(4):708–15.
16. Hoover P., Naz R.K. Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma? Int J Androl 2012 Aug;35(4):608–15.
17. Mirilas P., Panayiotides I., Mentessidou A. et al. Effect of testis nondescent or orchidopexy on antisperm antibodies and testis histology in rats. Fertil Steril 2010;94(4):1504–9.
18. Marconi M., Weidner W. Site and risk factors of antisperm antibodies production in the male population. Immune infertility. The impact of immune reaction on human infertility. Eds. W.K. Krause, R.K. Naz. Springer, 2009. Pp. 97–109.
19. WHO laboratory manual for the examination and processing of human semen. Fifth ed., WHO, 2010. 271 p.
20. Andrology: male reproductive health and disfunction. 3rd edition. Eds. E. Nieschlag, H.M. Behre, S. Nieschlag. Springer, 2010. R. 148.
21. Lee R., Goldstein M., Ullery B.W. et al. Experts’ comments: value of serum antisperm antibodies in diagnosing obstructive azoospermia. J Urol 2009;181:264–9.
22. Leonhartsberger N., Gozzi C., Akkad T. et al. Organ-sparing surgery does not lead to greater antisperm antibody levels than orchidectomy. BJU Int 2007;100:371–4.
23. Ozturk U., Ozdemir E., Dede O. et al. Assessment of anti-sperm antibodies in couples after testicular sperm extraction. Clin Invest Med 2011 Jun;34(3):E179–83.
24. Meil D., Brostoff Dzh., Rot D.B., Roit A. Immunologiya, 7-e izdanie. M., 2007. C. 236, 352–363.
25. Prabha V., Chaudhary N., Kaur S. Molecular mimicry between spermatozoa and bacteria. J Urol 2011 Dec;186(6):2442–7.
26. Jeremias J., Witkin S.S. Molecular approaches to the diagnosis of male infertility. Mol Hum Reprod 1996;2(3):195–202.
27. Bozhedomov V.A., Nikolaeva M.A. Golubeva E.L. i dr. Autoimmunnye reaktsii protiv spermatozoidov: epidemiologiya, etiopatogenez, diagnostika, lechenie. Muzhskoe zdorov'e i dolgoletie. 9-ya Mezhdunarodnaya meditsinskaya vystavka, 16–17 fevralya 2011 g., Moskva. Materialy foruma, 2011. S. 20–21.
28. Aitken R.J., Clarkson J.S., Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod 1989;41:183–97.
29. Zorn B., Vidmar G., Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm
30. injection. Int J Androl 2003;26:279–85.
31. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 2008;14(3):243–58.
32. Bozhedomov V.A., Gromenko D.S., Ushakova I.V. i dr. Prichiny oksidativnogo stressa spermatozoidov. Problemy reproduktsii 2008;6:67–73.
33. Nikolaeva M.A., Kulakov V.I., Korotkova I. et al. Antisperm antibodies detection by flow cytometry is affectid by aggregation of antigen-antibody complexes on the surfase of spermatozoa. Hum Reprod
34. ;15:2545–53.
35. Bozhedomov V.A., Nikolaeva M.A., Ushakova I.V. i dr. Rol' protsessov svobodno-radikal'nogo okisleniya v patogeneze muzhskogo immunnogo besplodiya. Androl i genit khir 2010;4:62–6.
36. Zini A., Fahmy N., Belzile E. et al. Antisperm antibodies are not associated with pregnancy rates after
37. IVF and ICSI: systematic review and meta-analysis. Hum Reprod 2011 Jun;26(6):1288–95.
