KaydedilenlerDerginizi ekleyin

Dergiler / Ankara Üniversitesi Eczacılık Fakültesi Dergisi / 2026 / Cilt: 50 Sayı: 3

ERKEK ÜREME SİSTEMİ TOKSİSİTESİNİN DEĞERLENDİRİLMESİNDE DENEY HAYVANLARINA ALTERNATİF YÖNTEMLER

ALTERNATIVE METHODS USING EXPERIMENTAL ANIMALS IN ASSESSING MALE REPRODUCTIVE SYSTEM TOXICITY

Merve Baysal(ANADOLU ÜNİVERSİTESİ)0000-0002-8099-0942
Abdullah Burak Karaduman(ANADOLU ÜNİVERSİTESİ)0000-0002-0434-1334
Büşra Korkut Çelikateş(ANADOLU ÜNİVERSİTESİ)0000-0003-0149-3065
Merve Güven(ANADOLU ÜNİVERSİTESİ)0009-0006-0836-664X
Sayfa
739–749
Yayın Tarihi
2026-09-19
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Daha iyi tasarlanmış, güvenilir modellere ihtiyaç duyulmaktadır.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Amaç: Bu derleme kapsamında erkek üreme sistemi toksisitesi çalışmalarında kullanılan geleneksel in vitro yöntemler, yenilikçi in vitro modeller ile değerlendirme süreçlerine entegre edilen in silico yaklaşımlardan bahsedilmiştir.
📊
Temel Bulgular & Veri:Sonuç ve Tartışma: Erkek üreme sistemi toksisitesi, spermatogenezis süreci ve spermatozoon fonksiyonları üzerinde olumsuz etkilere neden olan ekzojen ve endojen faktörleri kapsar.
💡
Sonuç & Katkı:Daha iyi tasarlanmış, güvenilir modellere ihtiyaç duyulmaktadır.
🔬Tür:Literatür & Derleme Çalışması
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Erkek üreme sistemi toksisitesi · in silico · in vitro

Özet

Amaç: Bu derleme kapsamında erkek üreme sistemi toksisitesi çalışmalarında kullanılan geleneksel in vitro yöntemler, yenilikçi in vitro modeller ile değerlendirme süreçlerine entegre edilen in silico yaklaşımlardan bahsedilmiştir. Sonuç ve Tartışma: Erkek üreme sistemi toksisitesi, spermatogenezis süreci ve spermatozoon fonksiyonları üzerinde olumsuz etkilere neden olan ekzojen ve endojen faktörleri kapsar. Seminifer epitel, Leydig ve Sertoli hücreleri, epididimal spermatozoa olgunlaşması ve endokrin sistem bu süreçte temel hedeflerdir. Günümüzde üreme toksisitesinin değerlendirilmesi genellikle in vivo yöntemlerle gerçekleştirilmektedir; ancak bu yöntemler yüksek maliyetli, zaman alıcı ve etik açıdan tartışmalıdır. Alternatif yaklaşımlara duyulan ihtiyaç, özellikle Avrupa’daki düzenlemeler kapsamında vurgulanmış, deney hayvanı kullanımını azaltmaya yönelik çalışmaların önemini artırmıştır. Üreme sürecinin çok aşamalı ve hassas bir yapıya sahip olması, toksisite değerlendirmesini karmaşık hale getirmektedir. Kullanılan in vivo ve in vitro yöntemler toksik etkileri öngörme konusunda sınırlı bir kapasiteye sahiptir. Daha iyi tasarlanmış, güvenilir modellere ihtiyaç duyulmaktadır.

Abstract

Objective: This review discusses traditional in vitro methods used in male reproductive toxicity studies, innovative in vitro models, and in silico approaches integrated into toxicity assessment processes. Result and Discussion: Male reproductive toxicity encompasses exogenous and endogenous factors that adversely affect spermatogenesis and sperm function. Key targets in this process include the seminiferous epithelium, Leydig and Sertoli cells, epididymal sperm maturation, and the endocrine system. Currently, the assessment of reproductive toxicity is predominantly conducted through in vivo methods; however, these approaches are costly, time-consuming, and ethically controversial. The need for alternative approaches has been particularly highlighted within the scope of regulations in Europe, increasing the importance of studies aimed at reducing the use of experimental animals. The multi-stage and highly sensitive nature of the reproductive process complicates toxicity assessment, and both in vivo and in vitro methods have limited predictive capacity. Therefore, there is a pressing need for well-designed and reliable models.

🔖

Bu Makaleye Atıf Yap

Baysal, M., Karaduman, A. B., Çelikateş, B. K., Güven, M. (2026). ERKEK ÜREME SİSTEMİ TOKSİSİTESİNİN DEĞERLENDİRİLMESİNDE DENEY HAYVANLARINA ALTERNATİF YÖNTEMLER. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, Cilt: 50 Sayı: 3, 739–749. https://doi.org/10.33483/jfpau.1650461

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (57)

  1. Sullivan, F.M. (1995). The European Community directive on the classification and labeling of chemicals for reproductive toxicity. Journal of Occupational and Environmental Medicine, 37(8), 966.
  2. Panga, J., Zhao, Y. (2024). Male reproductive toxicity of antifouling chemicals: Insights into oxidative stress-induced infertility and molecular mechanisms of zinc pyrithione (ZPT). Antioxidants, 13(2), 173. [CrossRef]
  3. Mantovani, A., Maranghi, F. (2005). Risk assessment of chemicals potentially affecting male fertility. Contraception, 72(4), 308-313. [CrossRef]
  4. Sakib, S., Voigt, A., Goldsmith, T., et al. (2019). Three-dimensional testicular organoids as novel in vitro models of testicular biology and toxicology. Environmental Epigenetics, 5(3), dvz011. [CrossRef]
  5. Lawson, C.C., Schnorr, T.M., Daston, G.P., et al. (2003). An occupational reproductive research agenda for the third millennium. Environmental Health Perspectives, 111(4), 584-592. [CrossRef]
  6. Jiang, C., Yang, H., Di, P., et al. (2019). In silico prediction of chemical reproductive toxicity using machine learning. Journal of Applied Toxicology, 39(6), 844-854. [CrossRef]
  7. Saldutti, L., Beyer, B.K., Breslin, W., et al. (2013). In vitro testicular toxicity models: Opportunities for advancement via biomedical engineering techniques. ALTEX, 30(3), 353-377. [CrossRef]
  8. Tornqvist, E., Annas, A., Granath, B., et al. (2014). Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing. PLoS One, 9, e101638. [CrossRef]
  9. Beekhuijzen, M. (2017). The era of 3Rs implementation in developmental and reproductive toxicity (DART) testing: Current overview and future perspectives. Reproductive Toxicology, 72, 86-96. [CrossRef]
  10. Park, S.R., Kook, M.G., Kim, et al. (2024). Development of a novel testis-on-a-chip that demonstrates reciprocal crosstalk between Sertoli and Leydig cells in testicular tissue. Experimental & Molecular Medicine, 56, 1591-1605. [CrossRef]
  11. Lamb, J.C., Chapin, R.E. (1993). Testicular and germ cell toxicity: In vitro approaches. Reproductive Toxicology, 7(Suppl 1), 17-22. [CrossRef]
  12. Tharmalingam, M.D., Jorgensen, A., Mitchell, R.T. (2018). Experimental models of testicular development and function using human tissue and cells. Molecular and Cellular Endocrinology, 468, 95-110. [CrossRef]
  13. Pendergraft, S.S., Sadri-Ardekani, H., Atala, A., et al. (2017). Three-dimensional testicular organoid: A novel tool for the study of human spermatogenesis and gonadotoxicity in vitro. Biology of Reproduction, 96(3), 720-732. [CrossRef]
  14. Duval, K., Grover, H., Han, L.H., et al. (2017). Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda, Md.), 32(4), 266-277. [CrossRef]
  15. Kapałczynska, M., Kolenda, T., Przybyła, et al. (2018). 2D and 3D cell cultures- a comparison of different types of cancer cell cultures. Archives of Medical Science, 14(4), 910-919. [CrossRef]
  16. Baker, B.M., Chen, C.S. (2012). Deconstructing the third dimension: How 3D culture microenvironments alter cellular cues. Journal of Cell Science, 125, 3015-3024. [CrossRef]
  17. Brevini, T.A., Pennarossa, G., Gandolfi, F. (2020). A 3D approach to reproduction. Theriogenology, 150, 2–7. [CrossRef]
  18. Bedard, P., Gauvin, S., Ferland, K., et al. (2020). Innovative human three-dimensional tissue-engineered models as an alternative to animal testing. Bioengineering, 7(3), 115. [CrossRef]
  19. Clair, E., Mesnage, R., Travert, C., et al. (2012). A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels. Toxicology in vitro: An International Journal Published in Association with BIBRA, 26(2), 269-279. [CrossRef]
  20. Zhang, X.F., Choi, Y.J., Han, J.W., et al. (2015). Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells. International Journal of Nanomedicine, 10, 1335-1357. [CrossRef]
  21. Legendre, A., Froment, P., Desmots, S., et al. (2010). An engineered 3D blood-testis barrier model for the assessment of reproductive toxicity potential. Biomaterials, 31(16), 4492-4505. [CrossRef]
  22. Yin, L., Wei, H., Liang, S., et al. (2017). From the cover: An animal-free in vitro three-dimensional testicular cell coculture model for evaluating male reproductive toxicants. Toxicological Sciences: An Official Journal of the Society of Toxicology, 159(2), 307-326. [CrossRef]
  23. Goers, L., Freemont, P., Polizzi, K.M. (2014). Co-culture systems and technologies: Taking synthetic biology to the next level. Journal of the Royal Society, Interface, 11(96), 20140065. [CrossRef]
  24. Yoo, J., Jung, Y., Char, K., et al. (2023). Advances in cell coculture membranes recapitulating in vivo microenvironments. Trends in Biotechnology, 41(2), 214-227. [CrossRef]
  25. Zhang, X., Wang, L., Zhang, X., et al. (2017). The use of KnockOut serum replacement (KSR) in three-dimensional rat testicular cells co-culture model: An improved male reproductive toxicity testing system. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 106(Pt A), 487-495. [CrossRef]
  26. Harris, S., Shubin, S.P., Wegner, S., et al. (2016). The presence of macrophages and inflammatory responses in an in vitro testicular co-culture model of male reproductive development enhance relevance to in vivo conditions. Toxicology in vitro: An International Journal Published in Association with BIBRA, 36, 210-215. [CrossRef]
  27. Sharma, S., Venzac, B., Burgers, T., et al. (2022). Testis-on-chip platform to study ex vivo primate spermatogenesis and endocrine dynamics. Organs-on-a-Chip, 4, 100023. [CrossRef]
  28. Shuchat, S., Yossifon, G., Huleihel, M. (2022). Perfusion in organ-on-chip models and its applicability to the replication of spermatogenesis in vitro. International Journal of Molecular Sciences, 23(10), 5402. [CrossRef]
  29. Beißner, N., Reichl, S., Lorenz, T. (2016). Organ-on-chip. In S. van den Driesche, C. Ehrhardt (Eds.), Micro systems for pharmatechnology, Springer, 299-339. [CrossRef]
  30. Komeya, M., Kimura, H., Nakamura, H., et al. (2016). Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device. Scientific Reports, 6, 21472. [CrossRef]
  31. Vijayavenkataraman, S., Yan, W.C., Lu, W.F., et al. (2018). 3D bioprinting of tissues and organs for regenerative medicine. Advanced Drug Delivery Reviews, 132, 296-332. [CrossRef]
  32. Zhao, Y., Liu, Y., Dai, Y., et al. (2022). Application of 3D bioprinting in urology. Micromachines, 13(7), 1073. [CrossRef]
  33. Horvath-Pereira, B.O., Almeida, G.H.D.R., da Silva Júnior, L.N., et al. (2023). Biomaterials for testicular bioengineering: How far have we come and where do we have to go? Frontiers in Endocrinology, 14, 1085872. [CrossRef]
  34. Aydin, S., Yaşlı, M., Yildiz, Ş., et al. (2024). Advancements in three-dimensional bioprinting for reproductive medicine: A systematic review. Reproductive Biomedicine Online, 49(4), 104273. [CrossRef]
  35. Scarritt, M.E., Pashos, N.C., Bunnell, B.A. (2015). A review of cellularization strategies for tissue engineering of whole organs. Frontiers in Bioengineering and Biotechnology, 3, 43. [CrossRef]
  36. Krtolica, A., Giritharan, G. (2010). Use of human embryonic stem cell-based models for male reproductive toxicity screening. Systems Biology in Reproductive Medicine, 56(3), 213-221. [CrossRef]
  37. Kleinstreuer, N.C., Smith, A.M., West, P.R., et al. (2011). Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics. Toxicology and Applied Pharmacology, 257(1), 111-121. [CrossRef]
  38. Clark, A.T., Bodnar, M.S., Fox, M., et al. (2004). Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Human Molecular Genetics, 13(7), 727-739. [CrossRef]
  39. Nayernia, K., Nolte, J., Michelmann, H.W., et al. (2006). In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice. Developmental Cell, 11(1), 125-132. [CrossRef]
  40. Russell, L.D., Ettlin, R.A., Hikim, A.P.S., et al. (1993). Histological and histopathological evaluation of the testis. International Journal of Andrology, 16, 83. [CrossRef]
  41. Martin, L.A., Seandel, M. (2013). Propagation of adult SSCs: From mouse to human. Biomedical Research International, 2013, 384734. [CrossRef]
  42. Sanou, I., van Maaren, J., Eliveld, J., et al. (2022). Spermatogonial stem cell-based therapies: Taking preclinical research to the next level. Frontiers in Endocrinology, 13, 850219. [CrossRef]
  43. He, Z., Kokkinaki, M., Jiang, J., et al. (2010). Isolation, characterization, and culture of human spermatogonia. Biology of Reproduction, 82(2), 363-372. [CrossRef]
  44. Ibtisham, F., Honaramooz, A. (2020). Spermatogonial stem cells for in vitro spermatogenesis and in vivo restoration of fertility. Cells, 9(3), 745. [CrossRef]
  45. Zhang, R., Sun, J., Zou, K. (2016). Advances in isolation methods for spermatogonial stem cells. Stem Cell Reviews and Reports, 12(1), 15-25. [CrossRef]
  46. Aponte, P.M., van Bragt, M.P., de Rooij, D.G., et al. (2005). Spermatogonial stem cells: Characteristics and experimental possibilities. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 113(11-12), 727-742. [CrossRef]
  47. Kavlock, R.J., Ankley, G., Blancato, J., et al. (2008). Computational toxicology-A state of the science mini review. Toxicological Sciences, 103(1), 14-27. [CrossRef]
  48. Sarigiannis, D.A., Stratidakis, A.K., Karakitsios, S.P. (2024). In Silico Methods and In Silico Toxicology. Ed: Wexler, P. Encyclopedia of Toxicology, Elsevier, New York, 503-507. [CrossRef]
  49. Casey, W., Jacobs, A., Maull, E., et al. (2015). A new path forward: The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and National Toxicology Program’s Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). Journal of the American Association for Laboratory Animal Science, 54(2), 170-173.
  50. Valerio, L.G., Jr. (2009). In silico toxicology for the pharmaceutical sciences. Toxicology and Applied Pharmacology, 241(3), 356-370. [CrossRef]
  51. Matthews, E.J., Kruhlak, N.L., Cimino, M.C., et al. (2006). An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods. Regulatory Toxicology and Pharmacology, 44(2), 97-110. [CrossRef]
  52. Feng, H., Zhang, L., Li, S., et al. (2021). Predicting the reproductive toxicity of chemicals using ensemble learning methods and molecular fingerprints. Toxicology Letters, 340, 4-14. [CrossRef]
  53. Weyrich, A., Joel, M., Lewin, G., et al. (2022). Review of the state of science and evaluation of currently available in silico prediction models for reproductive and developmental toxicity: A case study on pesticides. Birth Defects Research, 114(14), 812-842. [CrossRef]
  54. Zhang, H., Shen, C., Liu, R., et al. (2020). Developing novel in silico prediction models for assessing chemical reproductive toxicity using the naïve Bayes classifier method. Journal of Applied Toxicology, 40(9), 1198-1209. [CrossRef]
  55. Stojilković, N., Radović, B., Vukelić, D., et al. (2023). Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining. Environmental Research, 238, 117274. [CrossRef]
  56. Marzo, M., Roncaglioni, A., Kulkarni, S., et al. (2022). In Silico Models for Developmental Toxicity. Ed: Benfenati E. In Silico Methods for Predicting Drug Toxicity, 2425, Humana Press, New York, 217-240. [CrossRef]
  57. Luijten, M., de Vries, A., Opperhuizen, A., et al. (2008). Alternative methods in reproductive toxicity testing: State of the art. RIVM Report 340720002.