TY  - JOUR
T1  - Seasonal Variation in TLR4 Expression in The Testis and Epididymis of Anatolian Ground Squirrels (Spermophilus xanthoprymnus): Insights from Non-Breeding Period of Pre-Hibernation and Hibernation
TT  - Anadolu Yer Sincaplarının (Spermophilus xanthoprymnus) Testis ve Epididimisinde TLR4 Ekspresyonundaki Dönemsel Değişiklikler: Üreme Dışı pre-Hibernasyon ve Hibernasyon Dönemlerinden Elde Edilen Bulgular
AU  - Özbek, Mehmet
PY  - 2024
DA  - September
Y2  - 2024
DO  - 10.30607/kvj.1499739
JF  - Kocatepe Veterinary Journal
JO  - kvj
PB  - Afyon Kocatepe University
WT  - DergiPark
SN  - 1308-1594
SP  - 280
EP  - 288
VL  - 17
IS  - 3
LA  - en
AB  - This study investigates the modulation of Toll-like receptor 4 (TLR4) expression within the testis and epididymis of Anatolian ground squirrels (Spermophilus xanthoprymnus) during the non-breeding period of pre-hibernation and hibernation. Immunohistochemical investigation showed that TLR4 was not detected in germ cells, Leydig cells, or Sertoli cells in the testicular tissue during the pre-hibernation period. Nevertheless, there was a presence of TLR4 in the vessels walls and certain interstitial cells within the intertubular regions. Epithelial cells in the caput, corpus, and cauda regions of the epididymis showed no TLR4 expression. However, it was observed in the vessel walls, smooth muscle layers, and some interstitial cells. TLR4 expression was seen in spermatogonia and primary spermatocytes during hibernation, with strong labeling observed in the vessel walls of the intertubular area. In contrast, TLR4 was detected in the epididymal epithelium, as well as in the smooth muscle layers and vessel walls throughout all segments. A notable upregulation in the expression of TLR4 in the testis was identified through quantitative image analysis during hibernation as compared to pre-hibernation. During pre-hibernation, the cauda segment of the epididymis exhibited the highest expression of TLR4, whereas during hibernation, the corpus segment demonstrated the highest expression. These findings suggest a dynamic modulation of TLR4 in response to hibernation, highlighting its potential role in reproductive function and immune adaptation.
KW  - TLR4
KW  - Testis
KW  - Epididymis
KW  - Spermophilus xanthoprymnus
N2  - Bu çalışma, üreme dışı dönemde pre-hibernasyon ve hibernasyon süresince Anadolu yer sincaplarının (Spermophilus xanthoprymnus) testis ve epididimis dokularında Toll-like reseptör 4 (TLR4) ekspresyonunun regülasyonunu araştırmaktadır. İmmünohistokimyasal inceleme, TLR4'ün pre-hibernasyon döneminde testis dokusundaki germ hücreleri, Leydig hücreleri ve Sertoli hücrelerinde tespit edilmediğini göstermiştir. Bununla birlikte, intertubuler alandaki damar duvarlarında ve bazı interstisyel hücrelerde TLR4 mevcuttur. Epididimisin kaput, korpus ve kauda bölgelerindeki epitel hücrelerinde TLR4 ekspresyonu gözlenmemiştir. Ancak, damar duvarlarında, düz kas ve bazı interstisyel hücrelerde TLR4 mevcuttur. Hibernasyon sırasında, spermatogonyum ve primer spermatositlerde TLR4 ekspresyonu gözlenmiş olup, tübüller arası alanın damar duvarlarında güçlü bir immun reaksiyon görülmüştür. Buna karşılık, epididimisin bütün bölümlerindeki epitelinde, düz kas hücrelerinde ve damar duvarlarında TLR4 tespit edilmiştir. Hibernasyon döneminde, pre-hibernasyona kıyasla testiste TLR4 ekspresyonunda anlamlı bir artış, kantitatif görüntü analizi ile tespit edilmiştir. Pre-hibernasyon döneminde epididimisin kauda segmenti en yüksek TLR4 ekspresyonunu gösterirken, hibernasyon sırasında korpus segmenti en yüksek ekspresyonu göstermiştir. Bu bulgular, hibernasyona yanıt olarak TLR4'ün dinamik bir şekilde düzenlendiğini göstermekte olup, bu reseptörün üreme fonksiyonu ve bağışıklık adaptasyonundaki potansiyel rolüne işaret etmektedir.
CR  - Akira, S., Uematsu, S., & Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell, 124(4), 783–801. https://doi.org/10.1016/J.CELL.2006.02.015
CR  - Beutler, B. (2009). Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunological Reviews, 227(1), 248–263. https://doi.org/10.1111/J.1600-065X.2008.00733.X
CR  - Bouma, H. R., Carey, H. V, & Kroese, F. G. M. (2010). Hibernation: the immune system at rest? Journal of Leukocyte Biology, 88(4), 619–624. https://doi.org/10.1189/JLB.0310174
CR  - Carey, H. V., Andrews, M. T., & Martin, S. L. (2003). Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiological Reviews, 83(4), 1153–1181. 
https://doi.org/10.1152/PHYSREV.00008.2003
CR  - Fijak, M., & Meinhardt, A. (2006). The testis in immune privilege. Immunological Reviews, 213(1), 66–81. https://doi.org/10.1111/J.1600-065X.2006.00438.X
CR  - Giroud, S., Habold, C., Nespolo, R. F., Mejías, C., Terrien, J., Logan, S. M., Henning, R. H., & Storey, K. B. (2020). The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms†. Frontiers in Physiology, 11. https://doi.org/10.3389/FPHYS.2020.623665
CR  - Gu, X., Li, S. Y., & DeFalco, T. (2022). Immune and vascular contributions to organogenesis of the testis and ovary. The FEBS Journal, 289(9), 2386–2408. https://doi.org/10.1111/FEBS.15848
CR  - Gür, H., & Kart Gür, M. (2005). Annual Cycle of Activity, Reproduction, and Body Mass of Anatolian Ground Squirrels (Spermophilus xanthoprymnus) in Turkey. Journal of Mammalogy, 86(1), 7–14. 
https://doi.org/https://doi.org/10.1644/1545-1542(2005)086 <0007:ACOARA>2.0.CO;2
CR  - Hargreaves, D. C., & Medzhitov, R. (2005). Innate sensors of microbial infection. Journal of Clinical Immunology, 25(6), 503–510. https://doi.org/10.1007/S10875-005-8065-4
CR  - Hedger, M. P. (2011a). Immunophysiology and Pathology of Inflammation in the Testis and Epididymis. Journal of Andrology, 32(6), 625–640. https://doi.org/10.2164/JANDROL.111.012989
CR  - Hedger, M. P. (2011b). Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—a perspective. Journal of Reproductive Immunology, 88(2), 130. https://doi.org/10.1016/J.JRI.2011.01.010
CR  - Hedger, M. P. (2015). The Immunophysiology of Male Reproduction. Knobil and Neill’s Physiology of Reproduction, 1, 805. https://doi.org/10.1016/B978-0-12-397175-3.00019-3
CR  - Heinrich, A., & DeFalco, T. (2020). Essential roles of interstitial cells in testicular development and function. Andrology, 8(4), 903–914. https://doi.org/10.1111/ANDR.12703
CR  - Hermo, L., & Robaire, B. (2002). Epididymal Cell Types and Their Functions. The Epididymis: From Molecules to Clinical Practice, 81–102. https://doi.org/10.1007/978-1-4615-0679-9_5
CR  - Hu, L., Li, Q., Yang, P., Gandahi, J. A., Arain, T. S., Le, Y., Zhang, Q., Liu, T., Y. Waqas, M., Ahmad, N., Liu, Y., & Chen, Q. (2016). Expression of TLR2/4 on Epididymal Spermatozoa of the Chinese Soft-Shelled Turtle Pelodiscus 
sinensis During the Hibernation Season. The Anatomical Record, 299(11), 1578–1584. https://doi.org/10.1002/AR.23463
CR  - Iwasaki, A., & Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nature Immunology, 5(10), 987–995. https://doi.org/10.1038/NI1112
CR  - Janeway, C. A., & Medzhitov, R. (2002). Innate immune recognition. Annual Review of Immunology, 20, 197–216. https://doi.org/10.1146/ANNUREV.IMMUNOL.20.083001.084359
CR  - Jensen, K., Krusenstjerna-Hafstrøm, R., Lohse, J., Petersen, K. H., & Derand, H. (2017). A novel quantitative immunohistochemistry method for precise protein measurements directly in formalin-fixed, paraffin-embedded specimens: analytical performance measuring HER2. Modern Pathology, 30(2), 180–193. https://doi.org/10.1038/MODPATHOL.2016.176
CR  - Kart Gür, M., Refinetti, R., & Gür, H. (2009). Daily rhythmicity and hibernation in the Anatolian ground squirrel under natural and laboratory conditions. Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology, 179(2), 155–164. https://doi.org/10.1007/S00360-008-0298-0/FIGURES/8
CR  - Kawai, T., & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology, 11(5), 373–384. https://doi.org/10.1038/NI.1863
CR  - Kawasaki, T., & Kawai, T. (2014). Toll-like receptor signaling pathways. Frontiers in Immunology, 5(SEP). https://doi.org/10.3389/FIMMU.2014.00461
CR  - Li, N., Wang, T., & Han, D. (2012). Structural, cellular and molecular aspects of immune privilege in the testis. Frontiers in Immunology, 3(JUN). https://doi.org/10.3389/FIMMU.2012.00152
CR  - Li, Q., Hu, L., Yang, P., Zhang, Q., Waqas, Y., Liu, T., Zhang, L., Wang, S., Chen, W., Le, Y., Ullah, S., & Chen, Q. (2015). Expression of TLR2/4 in the sperm-storing oviduct of the Chinese soft-shelled turtle Pelodiscus sinensis during hibernation season. Ecology and Evolution, 5(19), 4466–4479. https://doi.org/10.1002/ECE3.1726
CR  - Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nature Reviews. Immunology, 1(2), 135–145. https://doi.org/10.1038/35100529
CR  - Meinhardt, A., & Hedger, M. P. (2011). Immunological, paracrine and endocrine aspects of testicular immune privilege. Molecular and Cellular Endocrinology, 335(1), 60–68. https://doi.org/10.1016/J.MCE.2010.03.022
CR  - Olson, M. E., & McCabe, K. (1986). Anesthesia in the Richardson’s ground squirrel: comparison of ketamine, ketamine and xylazine, droperidol and fentanyl, and sodium pentobarbital. Journal of the American Veterinary Medical Association, 189(9), 1035–1037. https://europepmc.org/article/med/3505921
CR  - O’Neill, L. A. J., & Bowie, A. G. (2007). The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nature Reviews. Immunology, 7(5), 353–364. https://doi.org/10.1038/NRI2079
CR  - Özbek, M., Hitit, M., Öztop, M., Beyaz, F., Ergün, E., & Ergün, L. (2019). Spatiotemporal expression patterns of natriuretic peptides in rat testis and epididymis during postnatal development. Andrologia, 51(10), e13387. https://doi.org/10.1111/AND.13387
Öztop, M., Özbek, M., Liman, N., Beyaz, F., Ergün, E., & Ergün, L. (2019). Localization profiles of natriuretic peptides in hearts of pre-hibernating and hibernating Anatolian ground squirrels (Spermophilus xanthoprymnus). 
Veterinary Research Communications, 43(2), 45–65. https://doi.org/10.1007/S11259-019-9745-5/FIGURES/14
Saeidi, S., Shapouri, F., Amirchaghmaghi, E., Hoseinifar, H., Sabbaghian, M., Sadighi Gilani, M. A., Pacey, A. A., & Aflatoonian, R. (2014). Sperm protection in the male reproductive tract by Toll-like receptors. Andrologia, 46(7), 784–790. https://doi.org/10.1111/AND.12149
CR  - Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805–820. https://doi.org/10.1016/J.CELL.2010.01.022
CR  - Tung, K. S. K., Han, D., & Duan, Y. G. (2022). Editorial: The immunology of the male genital tract. Frontiers in Immunology, 13. https://doi.org/10.3389/FIMMU.2022.1042468
CR  - van Breukelen, F., & Martin, S. L. (2015). The Hibernation Continuum: Physiological and Molecular Aspects of Metabolic Plasticity in Mammals. Physiology (Bethesda, Md.), 30(4), 273–281. 
https://doi.org/10.1152/PHYSIOL.00010.2015
CR  - Wang, F., Chen, R., Han, D., Wang, F., Chen, R., & Han, D. (2019). Innate Immune Defense in the Male Reproductive System and Male Fertility. Innate Immunity in Health and Disease. https://doi.org/10.5772/INTECHOPEN.89346
CR  - Zhao, S., Zhu, W., Xue, S., & Han, D. (2014). Testicular defense systems: immune privilege and innate immunity. Cellular and Molecular Immunology, 11(5), 428. https://doi.org/10.1038/CMI.2014.38
UR  - https://doi.org/10.30607/kvj.1499739
L1  - https://dergipark.org.tr/en/download/article-file/3999313
ER  -