The alterations of blood-testis barrier in experimental testicular injury models

Abstract

The blood-testis barrier is found between the Sertoli cells and divides the seminiferous tubule epithelium into basal and adluminal compartments. The germinal cell renewal, differentiation and cell cycle progression up to the preleptotene spermatocytes stage take place in the basal compartment, however, meiosis, spermiogenesis and spermiation take place in the adluminal compertment. The blood-testis barrier consists of tight junctions as well as ectoplasmic specialisations, desmosomes and gap junctions to create specific microenvironment for the completion of spermatogenesis to form spermatozoa. The blood-testis barrier is not a static ultrastructure, it undergoes extensive restructuring during the seminiferous tubule epithelial cycle of spermatogenesis to allow the transit of preleptotene spermotocytes at the blood-testis barrier from basal compartment towards the adluminal compartment. The functions of the blood-testis barrier include preventing the transport of biomolecules into the paracellular space, forming an immunological barrier, separating cellular processes during the spermatogenic epithelial cycle, and establishing the cellular polarity of the seminiferous tubule. However, various environmental conditions, chemotherapeutic agents, toxic substances and lifestyle have degenerative effects on blood-testis barrier, resulting in testicular damage, altered sperm parameters and ultimately male infertility. The alterations in morphological and molecular organization of blood-testis barrier in different experimentally induced testis injury models are reviewed in this article.

Keywords

• Blood-testis barrier
• Sertoli cells
• Tight junction
• Testicular injury models

References

1. [1] Mruk DD, Cheng CY. The mammalian blood-testis barrier: Its biology and regulation. Endocr Rev 2015;36:564- 91. doi: 10.1210/er.2014-1101.
2. [2] Stanton PG. Regulation of the blood-testis barrier. Semin Cell Dev Biol 2016;59:166-73. doi: 10.1016/j. semcdb.2016.06.018.
3. [3] Franca LR, Hess RA, Dufour JM, Hofmann MC, Griswold MD. The Sertoli cell: One hundred fifty years of beauty and plasticity. Andrology 2016;4:189-212. doi: 10.1111/ andr.12165.
4. [4] Pelletier RM. The blood-testis barrier: The junctional permeability, the proteins and the lipids. Prog Histochem Cytochem. 2011;46:49-127. doi: 10.1016/j.proghi.2011.05.001
5. [5] Xia W, Mruk DD, Lee WM, Cheng CY. Cytokines and junction restructuring during spermatogenesis—a lesson to learn from the testis. Cytokine Growth Factor Rev 2005;16:469-93.
6. [6] Comhaire FH, Mahmoud AM, Depuydt CE, Zalata AA, Christophe ABB. Mechanisms and effects of male genital tract infection on sperm quality and fertilizing potential: the andrologist’s viewpoint. Hum Reprod Update 1999;5:393-8. doi: 10.1093/humupd/5.5.393.
7. [7] Shufaro Y, Prus D, Laufer N, Simon A. Impact of repeated testicular fine needle aspirations (TEFNA) and testicular sperm extraction (TESE) on the microscopic morphology of the testis: an animal model. Hum Reprod 2002 ;17:1795-9. doi: 10.1093/humrep/17.7.1795.
8. [8] Contuk G, Orun O, Demiralp-Eksioglu E, Ercan F. Morphological alterations and distribution of occludin in rat testes after bilateral vasectomy. Acta Histochem 2012;114:244- 51. doi: 10.1016/j.acthis.2011.06.006.

9. [9] Uribe P, Boguen R, Treulen F, Sánchez R, Villegas JV. Peroxynitrite-mediated nitrosative stress decreases motility and mitochondrial membrane potential in human spermatozoa. Mol Hum Reprod 2015;21:237-43. doi: 10.1093/ molehr/gau107.
10. [10] Uribe P, Cabrillana ME, Fornés MW, et al. Nitrosative stress in human spermatozoa causes cell death characterized by induction of mitochondrial permeability transition-driven necrosis. Asian J Androl 2018;20:600-7. doi: 10.4103/aja. aja_29_18.
11. [11] Erkanli Senturk G, Ersoy Canillioglu Y, Umay C, DemiralpEksioglu E, Ercan F. Distribution of Zonula Occludens-1 and Occludin and alterations of testicular morphology after in utero radiation and postnatal hyperthermia in rats. Int J Exp Pathol 2012;93:438-49. doi: 10.1111/j.1365-2613.2012.00844.x.
12. [12] Kolbasi B, Bulbul MV, Karabulut S, et al. Chronic unpredictable stress disturbs the blood-testis barrier affecting sperm parameters in mice. Reprod Biomed Online 2021 ;42:983-95. doi: 10.1016/j.rbmo.2020.12.007.
13. [13] Guvvala PR, Ravindra JP, Rajani CV, Sivaram M, Selvaraju S. Protective role of epigallocatechin-3-gallate on arsenic induced testicular toxicity in Swiss albino mice. Biomed Pharmacother 2017;96:685-94. doi: 10.1016/j. biopha.2017.09.151.
14. [14] Qiu L, Qian Y, Liu Z, et al. Perfluorooctane sulfonate (PFOS) disrupts blood-testis barrier by down-regulating junction proteins via p38 MAPK/ATF2/MMP9 signaling pathway. Toxicology 2016;373:1-12. doi: 10.1016/j. tox.2016.11.003.
15. [15] Elkin ND, Piner JA, Sharpe RM. Toxicant-induced leakage of germ cell-specific proteins from seminiferous tubules in the rat: Relationship to blood-testis barrier integrity and prospects for biomonitoring. Toxicol Sci 2010;117:439-48. doi: 10.1093/toxsci/kfq210.
16. [16] Selvaraju V, Baskaran S. Environmental contaminants and male infertility: Effects and mechanisms. Andrologia 2021;53:e13646. doi: 10.1111/and.13646
17. [17] Çanıllıoğlu YE, Ercan F. In utero etanol uygulamasının sıçan testis morfolojisi üzerine etkileri. ACU Sağlık Bil Derg 2011;2:10-6.
18. [18] Çanıllıoğlu YE. In utero etanol uygulamasının sıçan testis morfolojisi, hücre ölümü ve kan-testis bariyeri üzerine etkileri: infertilite açısından değerlendirilmesi. 4rd International Hippocrates Congress on Medical and Health Sciences. Abstract Book 2020;52-52.
19. [19] Tok OE, Ercan F. Cep telefonlarının yaydığı elektromanyetik dalgaların sıçan testis morfolojisi üzerine etkileri. Clin Exp Health Sci 2013;3:138-44.
20. [20] Tok. OE. Cep telefonlarının yaydığı elektromanyetik dalgaların sıçan testis gelişimi, hücre ölümü ve kan-testis bariyeri üzerine etkileri: İnfertilite açısından değerlendirme. [Master of Science Thesis]: Marmara University; 2013.
21. [21] Kiran D, Tok OE, Sehirli AO, Gokce AM, Ercan F. The morphological and biochemical investigation of electromagnetic wave effects on urinary bladder in prenatal rats. Marmara Med J 2017; 30: 146-54. doi:10.5472/ marumj.370642
22. [22] Akakin D, Tok OE, Anil D, et al. Electromagnetic waves from mobile phones may affect rat brain during development. Turk Neurosurg 2021;31:412-21. doi: 10.5137/1019-5149. JTN.31665-20.2.
23. [23] Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord 2015;13:423- 44. doi: 10.1089/met.2015.0095.
24. [24] World Health Organization (WHO). 2020. Obesity and Overweight. 2020. https://www.who.int/news-room/factsheets/detail/obesity-and-overweight. Accessed on: 23.10.2021
25. [25] Leisegang K, Sengupta P, Agarwal A, Henkel R. Obesity and male infertility: Mechanisms and management. Andrologia 2021;53:e13617. doi: 10.1111/and.13617
26. [26] Coskunlu B. Yüksek yağlı diyetle indüklenmiş obez sıçanlarda Myrthus communıs l. ekstraktının testis üzerine etkilerinin morfolojik ve biyokimyasal olarak değerlendirilmesi [Master of Science Thesis]: Marmara University; 2019.
27. [27] Elmas MA. Diyetle indüklenmiş obezitede egzersizin testis morfolojisi, hücre proliferasyonu ve kan testis bariyeri üzerine etkilerinin incelenmesi. [PhD Thesis]: Marmara University; 2018.
28. [28] Elmas MA, Arbak S, Ercan F. Ameliorating effects of exercise on disrupted epididymal sperm parameters in high fat diet-induced obese rats. Marmara Med J 2019; 32: 14-9 doi: 10.5472/marumj.518732
29. [29] Hersek İ. Yüksek yağlı diyetle indüklenmiş obez sıçanlarda aposininin testis üzerine etkisi: histolojik ve biyokimyasal değerlendirme [Master of Science Thesis]: Marmara University; 2019.
30. [30] Lee NP, Wong EW, Mruk DD, Cheng CY. Testicular cell junction: a novel target for male contraception. Curr Med Chem 2009;16:906-15. doi: 10.2174/092.986.709787549262.
31. [31] Wong CH, Mruk DD, Lui WY, Cheng CY. Regulation of blood-testis barrier dynamics: an in vivo study. J Cell Sci 2004;117(Pt 5):783-98. doi: 10.1242/jcs.00900.
32. [32] Fiorini C, Tilloy-Ellul A, Chevalier S, Charuel C, Pointis G. Sertoli cell junctional proteins as early targets for different classes of reproductive toxicants. Reprod Toxicol 2004;18:413- 21. doi: 10.1016/j.reprotox.2004.01.002.
33. [33] Koroglu KM, Cevik O, Sener G, Ercan F. Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia 2019;51:e13227. doi: 10.1111/and.13227.
34. [34] Özyılmaz Yay N, Şener G, Ercan F. Resveratrol treatment reduces apoptosis and morphological alterations in cisplatin induced testis damage. J Res Pharm 2019; 23: 621-31. doi:10.12991/jrp.2019.170