Elektronik Sigara Aerosollerinin Testis Dokusunda Seminifer Tübül Yapısı, Kan-Testis Bariyeri ve Steroidogenez Üzerine Histopatolojik Etkileri

Öz

Amaç: Bu derlemede e-sigara aerosolüne veya e-sıvıya maruz kalmanın testisler ve fertilite üzerindeki histopatolojik, steroidojenik, redoks ile ilgili fonksiyonel etkilerini değerlendirmek; aynı zamanda doğrudan e-sigara kanıtlarını, karşılaştırmalı mekanistik ve klinik bağlamdaki kanıtlardan ayırt etmek amaçlanmıştır. Materyal ve Metod: PubMed ve Web of Science very tabanlarında, Ocak 2016 ile Haziran 2026 tarihleri arasında yayınlanmış, hakemli İngilizce çalışmalar aranmıştır. Doğrudan e-sigara/e-sıvı testis çalışmaları, fertilite ve IVF/ ICSI verileri, derlemeler, karşılaştırmalı mekanistik modeller ve koruyucu müdahale çalışmaları anlatımsal olarak sentezlenmiştir. Yirmi beş kaynak belirtilen kapsamı karşılamıştır. Bulgular: Yapılan çalışmalar, e-sigara maruziyeti seminifer epitel hasarı, testis ağırlığı veya seminifer tübül çapında azalma, sperm hareketliliği ve canlılığında olumsuz etkiler, Leydig hücrelerinde steroidogenezde değişiklik, oksidatif stres ve apoptoz ile ilişkilendirmiştir. Sertoli hücre bağlantısı ve kan-testis bariyerinde bozulmaya dair kanıtlar daha sınırlı bulunmuştur ve mekanizmaya ilişkin birçok bulgu, doğrudan e-sigara maruziyetinden ziyade, sadece nikotin, sigara dumanı, ısıtılmış tütün veya kimyasal toksin modellerinden elde edilmiştir. Sonuç: E-sigaralar, nikotinsiz formülasyonlar kullanıldığında bile fertilite açısından zararsız olarak sunulmamalıdır. Bununla birlikte, heterojen maruz kalma modelleri ve hiç kullanmamış kontrol gruplarını içeren çalışmaların azlığı, kesin klinik çıkarımlara varılmasını engellemektedir.

Anahtar Kelimeler

• Elektronik sigara
• testis
• Seminifer tübül
• kan-testis bariyeri

Etik Beyan

Bu çalışma için Etik kurul onayı gerekmemektedir; çünkü bu çalışma bir derleme (narrative review) niteliğinde olup insan katılımcıları, deney hayvanları veya kimliği belirlenebilir kişisel verileri içermemektedir.

Histopathological Effects of E-Cigarette Aerosols on Seminiferous Tubule Structure, the Blood-Testis Barrier and Steroidogenesis in Testicular Tissue

Öz

Objective: To evaluate the histopathological, steroidogenic, redox-related and functional effects of e cigarette aerosol or e-liquid exposure on the testes and male fertility while distinguishing direct e cigarette evidence from comparative mechanistic and clinical-context evidence. Materials and Methods: PubMed and Web of Science were searched for peer-reviewed English papers published from January 2016 through June 2026. Direct e-cigarette/e-liquid testis studies, human fertility and IVF/ICSI data, reviews, comparative mechanistic models and protective-intervention studies were narratively synthesized. Twenty-five papers met the stated scope. Results: Direct studies associated exposure with seminiferous epithelial injury, reductions in testis weight or seminiferous-tubule diameter, adverse sperm motility and viability, altered Leydig-cell steroidogenesis, oxidative stress and apoptosis. Evidence for Sertoli-cell junction and blood-testis barrier disruption was more limited, and several mechanistic findings derived from nicotine-only, cigarette-smoke, heated-tobacco or chemical-toxicant models rather than direct e-cigarette exposure. Conclusion: E-cigarettes should not be presented as harmless with respect to male fertility, including when nicotine-free formulations are used. However, heterogeneous exposure models and the scarcity of longitudinal studies with never-user control groups prevent definitive clinical inference.

Anahtar Kelimeler

• Electronic cigarette
• testis
• seminiferous tubule
• blood-testis barrier

Etik Beyan

Ethical approval was not required, as this is a narrative review and did not involve human participants, animals or identifiable personal data.

Kaynakça

1. 1. Kaur, G., Pinkston, R., McLemore, B., Dorsey, W. C., & Batra, S. (2018). Immunological and toxicological risk assessment of e-cigarettes. European Respiratory Review, 27, 170119.
2. 2. Mears, M. J., Bandaru, P., Neczypor, E. W., Byun, M. K., Zhang, M., Gorr, M. W., Masso-Silva, J. A., Barnes, L., Perryman, A., Kumar, A. J., Hendel, J. M., Fuentes, A. L., Wold, L. E., & Crotty Alexander, L. E. (2026). Multisystem toxicity of e-cigarettes in preclinical and clinical studies: Pathophysiologic effects of e-cigarette aerosol exposures from head to toe. Annual Review of Pharmacology and Toxicology, 66(1), 325-352.
3. 3. Montjean, D., Godin Pagé, M.-H., Bélanger, M.-C., Benkhalifa, M., & Miron, P. (2023). An overview of e-cigarette impact on reproductive health. Life, 13(3), 827.
4. 4. Szumilas, K., Szumilas, P., Grzywacz, A., & Wilk, A. (2020). The effects of e-cigarette vapor components on the morphology and function of the male and female reproductive systems: A systematic review. International Journal of Environmental Research and Public Health, 17(17), 6152.
5. 5. Asadi, N., Bahmani, M., Kheradmand, A., & Rafieian-Kopaei, M. (2017). The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review. Journal of Clinical and Diagnostic Research, 11(5), IE01-IE05.
6. 6. Barbagallo, F., Assenza, M. R., Torrisi, F., Buonacquisto, A., & Pallotti, F. (2024). The smoky impact of nicotinic acetylcholine receptors on testicular function. Journal of Clinical Medicine, 13(17), 5097.
7. 7. Szabó, A., Nyirády, P., & Kopa, Z. (2025). Impact of lifestyle and environmental factors on fertility. Current Opinion in Urology, 35, 685-690.
8. 8. Amalia, N., Zhafira, F. A., Yunita, M. N., Sari, S. O. N., Herdiansyah, A. D., Pratika, S., Wardana, P. R., Zahro, F., & Rahmadani, A. A. (2025). Effects of nicotine-containing e-cigarette smoke on testicular histopathology in albino rats. Journal of Basic Medical Veterinary, 14(2), 184-191.

9. 9. El Golli, N., Rahali, D., Jrad-Lamine, A., Dallagi, Y., Jallouli, M., Bdiri, Y., Ba, N., Lebret, M., Rosa, J. P., El May, M., & El Fazaa, S. (2016). Impact of electronic-cigarette refill liquid on rat testis. Toxicology Mechanisms and Methods, 26(6), 417-424.
10. 10. Elsherif, R., Abdellah, N. Z., Hussein, O. A., & Shaltout, E. S. (2023). Evaluation of hazards of electronic-cigarette's liquid refill on testes of mice, complemented by histopathological and chromatographic analysis. Ultrastructural Pathology, 47(2), 90-103.
11. 11. Silitonga, H. T. H., Rambung, E., Sekarputri, C. H., Nugraheni, E. S., & Mel-lyanawati. (2024). The impact of conventional cigarettes, nicotine-containing, and nicotine-free electronic cigarettes on testicular weight of male Wistar rats. Buletin Poltanesa, 25(1), 140-146.
12. 12. Vivarelli, F., Canistro, D., Cirillo, S., Cardenia, V., Rodriguez-Estrada, M. T., & Paolini, M. (2019). Impairment of testicular function in electronic cigarette (e-cig, e-cigs) exposed rats under low-voltage and nicotine-free conditions. Life Sciences, 228, 53-65.
13. 13. Wawryk-Gawda, E., Zarobkiewicz, M. K., Chłapek, K., Chylińska-Wrzos, P., & Jodłowska-Jędrych, B. (2019). Histological changes in the reproductive system of male rats exposed to cigarette smoke or electronic cigarette vapor. Toxicological & Environmental Chemistry, 101(7-8), 404-419.
14. 14. Widianti, I. G. A., Wardana, N. G., Widhiartini, I. A. A., Satriyasa, B. K., Antari, N. W. S., & Pratiwi, M. S. A. (2026). The potential of Binahong leaf (Anredera cordifolia) ethanol extract on male fertility in mice exposed to e-cigarette smoke. Journal of Health and Nutrition Research, 5(1), 464-474.
15. 15. Zulfikar, M. A., Hestianah, E. P., Hermadi, H. A., Utama, S., Hernawati, T., Kuncorojakti, S., & Luqman, E. M. (2022). Effect of exposure to e-cigarette vapor and cigarette smoke on seminiferous tubules diameter and spermatozoa quality of mice (Mus musculus). Ecology, Environment and Conservation, 28(3), 1246-1251.
16. 16. Ardiantari, V. R., & Rizaldi, F. (2025). The Impact of Electronic Cigarettes on Male Fertility: A Literature Review. Indonesian Andrology & Biomedical Journal, 6(2), 1-5.
17. 17. Kim, H. K., Choi, W. Y., Lee, J. I., & Kim, T. J. (2025). Impact of conventional cigarette and electronic cigarette use on sperm quality and IVF/ICSI outcomes. Scientific Reports, 15, 23714.
18. 18. Nahak, T. M., & Pramesemara, I. G. N. (2023). Electronic cigarettes on sperm quality: Review in animal and human study. Indonesian Andrology and Biomedical Journal, 4(2), 71-78.
19. 19. Roztoczyńska, A., Jeńć-Magoń, A., Orzechowska, M., Jablonska, K., Paluch, P., Lesniewski, K., Pudźwa, J., Gibczynski, K., Król, A., & Orczyk, M. (2025). Analysis of awareness of the effects of electronic cigarettes on fertility. Medical Science, 29, e47ms3517.
20. 20. Dai, P., Ding, M., Yu, J., Gao, Y., Wang, M., Ling, J., Dong, S., Zhang, X., Zeng, X., & Sun, X. (2024). The male reproductive toxicity caused by 2-naphthylamine was related to testicular immunity disorders. Toxics, 12(5), 342.
21. 21. Granata, S., Morosini, C., Valerii, M. C., Fagiolino, I., Sangiorgi, S., Ghini, S., Spisni, E., Vivarelli, F., Fairclough, L. C., Paolini, M., & Canistro, D. (2025). Heat-not-burn technology affects plasma testosterone levels and markers of inflammation, oxidative stress in the testes of rats. Frontiers in Toxicology, 6, 1515850.
22. 22. Hazir, S., Yaroglu, H. Y., Bayram, G., & Askın, A. (2021). Investigation of the possible role of poly(ADP-ribose) polymerase pathway in nicotine-exposed testicular damage. Fresenius Environmental Bulletin, 30(06B), 7542-7550.
23. 23. Puspita, N. L. P. A. D. D. (2026). The effect of green tea (Camellia sinensis) infusion on Leydig cell count in testis of male Balb/C mice following electronic cigarette exposure. Journal of Social Research, 5(2), 474-480.
24. 24. Zayman, E., Gül, M., Erdemli, M. E., Gül, S., Gözükara Bağ, H., & Taşlıdere, E. (2022). Biochemical and histopathological investigation of the protective effects of melatonin and vitamin E against the damage caused by acetamiprid in Balb-c mouse testicles at light and electron microscopic level. Environmental Science and Pollution Research, 29, 47571-47584.
25. 25. Zhong, Y., Wei, X., Yasin, Z., Huang, Y., & He, L. (2026). Cigarette smokeexposure disrupts the blood-testis barrier and negatively impacts reproductive capacity in mice. Toxicology, 522, 154407