Yeni Koronavirüs (SARS-CoV-2) ilk olarak Çin’in Vuhan şehrinde ortaya çıkmış ve Yeni Koronavirüs Hastalığı’na (Covid-19) neden olmuştur. Covid-19 dünya çapında hızla yayılmakta ve vaka sayısı tüm ülkelerde artmaktadır. 22 Kasım verilerine göre dünya genelinde vaka sayısının 57.8 milyonu geçtiği ve 1.3 milyon kişinin hayatını kaybettiği bildirilmiştir. SARS‐CoV‐2’nin, hücrelere girmek için bir reseptör olarak anjiyotensin-dönüştürücü enzim 2’yi (ACE2) kullandığı bilinmektedir. ACE2 ekspresyon dağılımının organa özgü olduğu, testis ve böbrek dokuları başta olmak üzere kardiyovasküler ve gastrointestinal sistemde de bulunduğu belirtilmiştir. ACE2 reseptörlerinin ekspresyonu hem erkek hem de dişi üreme organlarında yer almaktadır. SARS‐CoV‐2’nin enfeksiyon oranları yaş gruplarına göre farklılık göstermektedir. Erkekler kadınlardan daha yüksek hastalık prevalansına sahiptir. Normal testis dokularında ACE2 antikorunun kullanıldığı immünohistokimyasal (İHK) analizlerde, seminifer tübül ve Leydig hücrelerinde yüksek boyanmaya neden olduğu görülmüştür. SARS‐CoV‐2’den etkilenen hücrelerin spermatogenezi engelleyeceği ve erkek infertilitesine neden olabileceği belirtilmiştir. SARS-CoV-2’nin üreme sistemini etkileme düzeyini belirlemek oldukça güçtür. Bu hastalığın tedavisinde kullanılacak kesin bir ilaç veya aşı olmadığı için, çalışmaların uzun bir süre devam edeceği ve daha çok şey öğreneceğimiz düşünülmektedir
Ashour, M. H., Elkhatib, F. W., Rahman, M. M. ve Elshabrawy, A. H. (2020). Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathogens, 9(3), 186.
Batiha, O., Al-Deeb, T., Al-zoubi, E. ve Alsharu, E. (2020). Impact of COVID-19 and other viruses on reproductive health. Andrologia, 52(9), e13791.
Boopathi, S., Poma, A. B. ve Kolandaivel, P. (2020). Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn, 1-10.
Channappanavar, R., Fett, C., Mack, M., Ten Eyck, P. P., Meyerholz, D. K. ve Perlman, S. (2017). Sex-based differences in susceptibility to Severe Acute Respiratory Syndrome coronavirus infection. J Immunol, 198(10), 4046-4053.
de Wit, E., van Doremalen, N., Falzarano, D. ve Munster, V. J. (2016). SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol, 14(8), 523-534. doi:10.1038/nrmicro.2016.81
Dutta, S., Majzoub, A. ve Agarwal, A. (2019). Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J Urol, 17(2), 87-97.
Dutta, S. ve Sengupta, P. (2020). SARS-CoV-2 and male infertility: Possible multifaceted pathology. Reprod Sci, 1-4.
Esper, F., Weibel, C., Ferguson, D., Landry, M. L. ve Kahn, J. S. (2006). Coronavirus HKU1 infection in the United States. Emerg Infect Dis, 12(5), 775-779.
Fan, C., Li, K., Ding, Y., Lu, W. L. ve Wang, J. (2020). ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv, In press.
Fu, J., Zhou, B., Zhang, L., Balaji, K. S., Wei, C., Liu, X., … Fu, J. (2020). Expressions and significances of the angiotensin-converting enzyme 2 gene, the receptor of SARS-CoV-2 for covid-19. Mol Biol Rep, 47(6), 4383-4392.
Guarner, J. (2020). Three emerging coronaviruses in two decades. Am J Clin Pathol, 153(4), 420-421.
Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., … Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (covid-19) outbreak-an update on the status. Mil Med Res, 7(1), 11.
Harmer, D., Gilbert, M., Borman, R. ve Clark, K. L. (2002). Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett, 532(1-2), 107-110.
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., … Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271-280.e8.
Hsu, A. L., Finlinson, A. ve Warncke, K. (2020). Mechanisms by which SARS-CoV-2 may impact male fertility. Reprod Sci, 1-2.
Illiano, E., Trama, F. ve Costantini, E. (2020). Could covid-19 have an impact on male fertility? Andrologia, 52, e13654.
Jung, A. ve Schuppe, H. C. (2007). Influence of genital heat stress on semen quality in humans. Andrologia, 39(6), 203-215.
Karlberg, J., Chong, D. S. Y. ve Lai, W. Y. Y. (2004). Do men have a higher case fatality rate of Severe Acute Respiratory Syndrome than women do? Am J Epidemiol, 159(3), 229-231.
Khalili, M. A., Leisegang, K., Majzoub, A., Finelli, R., Selvam, M. K. P., Henkel, R., … Agarwal, A. (2020). Male fertility and the covid-19 pandemic: Systematic review of the literature. World J Mens Health, 38(4), 506-520.
Li, R., Yin, T., Fang, F., Li, Q., Chen, J., Wang, Y., … Qiao, J. (2020). Potential risks of SARS-CoV-2 infection on reproductive health. Reprod Biomed Online, 41(1), 89-95.
Lin, S.-Y. ve Chen, H.-W. (2017). Infectious bronchitis virus variants: Molecular analysis and pathogenicity investigation. Int J Mol Sci, 18(10), 2030. 0
Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet, 395(10224), 565-574.
Lukassen, S., Chua, R. L., Trefzer, T., Kahn, N. C., Schneider, M. A., Muley, T., … Eils, R. (2020). SARS‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells. EMBO J, 39(10), e105114.
Ma, L., Xie, W., Li, D., Shi, L., Mao, Y., Xiong, Y., … Zhang, M. (2020). Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study. medRxiv, In press.
Rastrelli, G., Di Stasi, V., Inglese, F., Beccaria, M., Garuti, M., Di Costanzo, D., … Vignozzi, L. (2020). Low testosterone levels predict clinical adverse outcomes in SARS‐CoV‐2 pneumonia patients. Andrology, 1-11.
Reis, A. B., Araújo, F. C., Pereira, V. M., Dos Reis, A. M., Santos, R. A. ve Reis, F. M. (2010). Angiotensin (1-7) and its receptor mas are expressed in the human testis: Implications for male infertility. J Mol Histol, 41(1), 75-80.
Reis, F. M., Bouissou, D. R., Pereira, V. M., Camargos, A. F., Dos Reis, A. M. ve Santos, R. A. (2011). Angiotensin-(1-7), its receptor mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil Steril, 95(1), 176-181.
Sama, I. E., Ravera, A., Santema, B. T., Van Goor, H., Ter Maaten, J. M., Cleland, J. G. F., … Voors, A. A. (2020). Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur Heart J, 41(19), 1810-1817.
Schroeder, M., Tuku, B., Jarczak, D., Nierhaus, A., Bai, T., Jacobsen, H., … Gabriel, G. (2020). The majority of male patients with COVID-19 present low testosterone levels on admission to intensive care in Hamburg, Germany: a retrospective cohort study. medRxiv, In press.
Segars, J., Katler, Q., McQueen, D. B., Kotlyar, A., Glenn, T., Knight, Z., … Kawwass, J. F. (2020). Prior and novel coronaviruses, Coronavirus Disease 2019 (covid-19), and human reproduction: what is known? Fertil Steril, 113(6), 1140-1149.
Shastri, A., Wheat, J., Agrawal, S., Chaterjee, N., Pradhan, K., Goldfinger, M., … Shastri, J. (2020). Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs. medRxiv, In press.
Shen, Q., Xiao, X., Aierken, A., Liao, M. ve Hua, J. (2020). The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 Infection. J Cell Mol Med, (24), 9472-9477.
Shuttleworth, G. (2002). In vitro development of pig preantral follicles cultured in a serum-free medium and the effect of angiotensin II. Reproduction, 123(6), 807-818.
Singh, B., Gornet, M., Sims, H., Kisanga, E., Knight, Z. ve Segars, J. (2020). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) and its effect on gametogenesis and early pregnancy. Am J Reprod Immunol, 84:e13351.
Singh, V., Agrawal, N. K., Verma, R. ve Singh, K. (2017). HPG axis: The central regulator of spermatogenesis and male fertility. Male Infertility: Understanding, In Causes and Treatment (pp. 25-36). Springer Singapore.
Tyrrell, D. A. J. ve Bynoe, M. L. (1965). Cultivation of a novel type of common-cold virus in organ cultures. Br Med J, 1(5448), 1467-1470.
Vignozzi, L., Gacci, M., Cellai, I., Santi, R., Corona, G., Morelli, A., … Maggi, M. (2013). Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate, 73(8), 789-800.
World Health Organization. (2020). Weekly Epidemiological Update-24 November 2020. Erişim adresi https://www.who.int/publications/m/item/weekly-epidemiological-update, Erişim tarihi: 24.11.2020.
Xia, S., Liu, M., Wang, C., Xu, W., Lan, Q., Feng, S., … 2020, undefined. (2020). Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high. Cell Research, 30, 343-355.
Xu, J., Qi, L., Chi, X., Yang, J., Wei, X., Gong, E., … Gu, J. (2006). Orchitis: A complication of severe acute respiratory syndrome (SARS). Biol Reprod, 74(2), 410-416.
Zou, X., Chen, K., Zou, J., Han, P., Hao, J. ve Han, Z. (2020). Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med, (2), 185-192.
The Effects of SARS‐CoV‐2 on the Male Reproductive System
Year 2022,
Volume: 11 Issue: 1, 143 - 149, 28.02.2022
The New Coronavirus (SARS-CoV-2) first appeared in Wuhan, China and caused the New Coronavirus Disease (Covid-19). Covid-19 is spreading rapidly around the world and the number of cases is increasing in all countries. According to the data of 22 November, it has been reported that the number of cases exceeded 57.8 million and 1.3 million people died worldwide. SARS‐CoV‐2 is known to use angiotensin-converting enzyme 2 (ACE2) as a receptor to enter cells. It has been reported that the distribution of ACE2 expression is organ-specific, and it is found in the cardiovascular and gastrointestinal systems, especially in testes and kidney tissues. Expression of ACE2 receptors is located in both male and female reproductive organs. The infection rates of SARS‐CoV‐2 vary according to age groups. Men have a higher prevalence of the disease than women. In immunohistochemical (IHC) analyzes using ACE2 antibody in normal testicular tissues, it was observed that it caused high staining in seminiferous tubule and Leydig cells. It has been stated that cells affected by SARS‐CoV‐ 2 will inhibit spermatogenesis and cause male infertility. It is very difficult to determine the effect level of SARS-CoV-2 on the reproductive system. Since there is no definitive drug or vaccine to be used in the treatment of this disease, it is thought that the studies will continue for a long time and we will learn more.
Ashour, M. H., Elkhatib, F. W., Rahman, M. M. ve Elshabrawy, A. H. (2020). Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathogens, 9(3), 186.
Batiha, O., Al-Deeb, T., Al-zoubi, E. ve Alsharu, E. (2020). Impact of COVID-19 and other viruses on reproductive health. Andrologia, 52(9), e13791.
Boopathi, S., Poma, A. B. ve Kolandaivel, P. (2020). Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn, 1-10.
Channappanavar, R., Fett, C., Mack, M., Ten Eyck, P. P., Meyerholz, D. K. ve Perlman, S. (2017). Sex-based differences in susceptibility to Severe Acute Respiratory Syndrome coronavirus infection. J Immunol, 198(10), 4046-4053.
de Wit, E., van Doremalen, N., Falzarano, D. ve Munster, V. J. (2016). SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol, 14(8), 523-534. doi:10.1038/nrmicro.2016.81
Dutta, S., Majzoub, A. ve Agarwal, A. (2019). Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J Urol, 17(2), 87-97.
Dutta, S. ve Sengupta, P. (2020). SARS-CoV-2 and male infertility: Possible multifaceted pathology. Reprod Sci, 1-4.
Esper, F., Weibel, C., Ferguson, D., Landry, M. L. ve Kahn, J. S. (2006). Coronavirus HKU1 infection in the United States. Emerg Infect Dis, 12(5), 775-779.
Fan, C., Li, K., Ding, Y., Lu, W. L. ve Wang, J. (2020). ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv, In press.
Fu, J., Zhou, B., Zhang, L., Balaji, K. S., Wei, C., Liu, X., … Fu, J. (2020). Expressions and significances of the angiotensin-converting enzyme 2 gene, the receptor of SARS-CoV-2 for covid-19. Mol Biol Rep, 47(6), 4383-4392.
Guarner, J. (2020). Three emerging coronaviruses in two decades. Am J Clin Pathol, 153(4), 420-421.
Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., … Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (covid-19) outbreak-an update on the status. Mil Med Res, 7(1), 11.
Harmer, D., Gilbert, M., Borman, R. ve Clark, K. L. (2002). Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett, 532(1-2), 107-110.
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., … Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2), 271-280.e8.
Hsu, A. L., Finlinson, A. ve Warncke, K. (2020). Mechanisms by which SARS-CoV-2 may impact male fertility. Reprod Sci, 1-2.
Illiano, E., Trama, F. ve Costantini, E. (2020). Could covid-19 have an impact on male fertility? Andrologia, 52, e13654.
Jung, A. ve Schuppe, H. C. (2007). Influence of genital heat stress on semen quality in humans. Andrologia, 39(6), 203-215.
Karlberg, J., Chong, D. S. Y. ve Lai, W. Y. Y. (2004). Do men have a higher case fatality rate of Severe Acute Respiratory Syndrome than women do? Am J Epidemiol, 159(3), 229-231.
Khalili, M. A., Leisegang, K., Majzoub, A., Finelli, R., Selvam, M. K. P., Henkel, R., … Agarwal, A. (2020). Male fertility and the covid-19 pandemic: Systematic review of the literature. World J Mens Health, 38(4), 506-520.
Li, R., Yin, T., Fang, F., Li, Q., Chen, J., Wang, Y., … Qiao, J. (2020). Potential risks of SARS-CoV-2 infection on reproductive health. Reprod Biomed Online, 41(1), 89-95.
Lin, S.-Y. ve Chen, H.-W. (2017). Infectious bronchitis virus variants: Molecular analysis and pathogenicity investigation. Int J Mol Sci, 18(10), 2030. 0
Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet, 395(10224), 565-574.
Lukassen, S., Chua, R. L., Trefzer, T., Kahn, N. C., Schneider, M. A., Muley, T., … Eils, R. (2020). SARS‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells. EMBO J, 39(10), e105114.
Ma, L., Xie, W., Li, D., Shi, L., Mao, Y., Xiong, Y., … Zhang, M. (2020). Effect of SARS-CoV-2 infection upon male gonadal function: A single center-based study. medRxiv, In press.
Rastrelli, G., Di Stasi, V., Inglese, F., Beccaria, M., Garuti, M., Di Costanzo, D., … Vignozzi, L. (2020). Low testosterone levels predict clinical adverse outcomes in SARS‐CoV‐2 pneumonia patients. Andrology, 1-11.
Reis, A. B., Araújo, F. C., Pereira, V. M., Dos Reis, A. M., Santos, R. A. ve Reis, F. M. (2010). Angiotensin (1-7) and its receptor mas are expressed in the human testis: Implications for male infertility. J Mol Histol, 41(1), 75-80.
Reis, F. M., Bouissou, D. R., Pereira, V. M., Camargos, A. F., Dos Reis, A. M. ve Santos, R. A. (2011). Angiotensin-(1-7), its receptor mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil Steril, 95(1), 176-181.
Sama, I. E., Ravera, A., Santema, B. T., Van Goor, H., Ter Maaten, J. M., Cleland, J. G. F., … Voors, A. A. (2020). Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur Heart J, 41(19), 1810-1817.
Schroeder, M., Tuku, B., Jarczak, D., Nierhaus, A., Bai, T., Jacobsen, H., … Gabriel, G. (2020). The majority of male patients with COVID-19 present low testosterone levels on admission to intensive care in Hamburg, Germany: a retrospective cohort study. medRxiv, In press.
Segars, J., Katler, Q., McQueen, D. B., Kotlyar, A., Glenn, T., Knight, Z., … Kawwass, J. F. (2020). Prior and novel coronaviruses, Coronavirus Disease 2019 (covid-19), and human reproduction: what is known? Fertil Steril, 113(6), 1140-1149.
Shastri, A., Wheat, J., Agrawal, S., Chaterjee, N., Pradhan, K., Goldfinger, M., … Shastri, J. (2020). Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs. medRxiv, In press.
Shen, Q., Xiao, X., Aierken, A., Liao, M. ve Hua, J. (2020). The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 Infection. J Cell Mol Med, (24), 9472-9477.
Shuttleworth, G. (2002). In vitro development of pig preantral follicles cultured in a serum-free medium and the effect of angiotensin II. Reproduction, 123(6), 807-818.
Singh, B., Gornet, M., Sims, H., Kisanga, E., Knight, Z. ve Segars, J. (2020). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) and its effect on gametogenesis and early pregnancy. Am J Reprod Immunol, 84:e13351.
Singh, V., Agrawal, N. K., Verma, R. ve Singh, K. (2017). HPG axis: The central regulator of spermatogenesis and male fertility. Male Infertility: Understanding, In Causes and Treatment (pp. 25-36). Springer Singapore.
Tyrrell, D. A. J. ve Bynoe, M. L. (1965). Cultivation of a novel type of common-cold virus in organ cultures. Br Med J, 1(5448), 1467-1470.
Vignozzi, L., Gacci, M., Cellai, I., Santi, R., Corona, G., Morelli, A., … Maggi, M. (2013). Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate, 73(8), 789-800.
World Health Organization. (2020). Weekly Epidemiological Update-24 November 2020. Erişim adresi https://www.who.int/publications/m/item/weekly-epidemiological-update, Erişim tarihi: 24.11.2020.
Xia, S., Liu, M., Wang, C., Xu, W., Lan, Q., Feng, S., … 2020, undefined. (2020). Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high. Cell Research, 30, 343-355.
Xu, J., Qi, L., Chi, X., Yang, J., Wei, X., Gong, E., … Gu, J. (2006). Orchitis: A complication of severe acute respiratory syndrome (SARS). Biol Reprod, 74(2), 410-416.
Zou, X., Chen, K., Zou, J., Han, P., Hao, J. ve Han, Z. (2020). Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med, (2), 185-192.
Kanat Gülle
SULEYMAN DEMIREL UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF BASIC MEDICAL SCIENCES, DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY0000-0002-6337-8962Türkiye
Abdullah Sarman
BINGOL UNIVERSITY, HEALTH SERVICES VOCATIONAL SCHOOL, DEPARTMENT OF MEDICAL SERVICES AND TECHNIQUES, FIRST AND EMERGENCY AID0000-0002-5081-4593Türkiye
Sarman, E., Gülle, K., & Sarman, A. (2022). SARS‐CoV‐2’nin Erkek Üreme Sistemi Üzerindeki Etkileri. Balıkesir Sağlık Bilimleri Dergisi, 11(1), 143-149. https://doi.org/10.53424/balikesirsbd.832919