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Aghajanpour, F., Soltani, R., Afshar, A., Abbaszadeh, H.-A., Fathabadi, F. F., Moeinian, N., Aliaghaei, A., Nejad, A. D., Farahani, R. M., Norouzian, M., & Abdollahifar, M.-A. (2024). Sertoli cell-conditioned medium can improve blood-testis-barrier function and spermatogenesis in azoospermia mice induced by scrotal hyperthermia: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 22(1), 17–30. https://doi.org/10.18502/ijrm.v22i1.15238
https://doi.org/10.18502/ijrm.v22i1.15238
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authors
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Fakhroddin Aghajanpour
Fakhroddin Aghajanpour
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Reza Soltani
Reza Soltani
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Azar Afshar
Azar Afshar
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Hojjat-Allah Abbaszadeh
Hojjat-Allah Abbaszadeh
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Fatemeh Fadaei Fathabadi
Fatemeh Fadaei Fathabadi
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Nafiseh Moeinian
Nafiseh Moeinian
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Abbas Aliaghaei
Abbas Aliaghaei
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Ali Dehghani Nejad
Ali Dehghani Nejad
Department of Biology and Anatomical Sciences, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
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Reza Mastery Farahani
Reza Mastery Farahani
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Mohsen Norouzian
Mohsen Norouzian
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Mohammad-Amin Abdollahifar
Mohammad-Amin Abdollahifar
Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Published Date
- Feb 18, 2024
Sertoli cell-conditioned medium can improve blood-testis-barrier function and spermatogenesis in azoospermia mice induced by scrotal hyperthermia: An experimental study
Abstract
Background: An increase in the temperature of the testis is associated with damage to the epithelium of seminiferous tubules and disruption of sperm production.
Objective: The current study aimed to investigate the effect of the Sertoli cell-conditioned medium (SCCM) on the blood-testis-barrier associated genes and spermatogenesis process following scrotal hyperthermia.
Materials and Methods: In this experimental study, 40 adult NMRI mice (8 wk, 25–30 gr) were allocated into 4 groups: I) control, II) DMEM (10 μl Dulbecco’s Modified Eagle Medium), III) scrotal hyperthermia, and IV) scrotal hyperthermia+SCCM (10 μl SCCM). Hyperthermia was induced by placing the mice scrotum in water at 43°C for 20 min every other day for 10 days. Mice were treated every other day for 5 wk. Then the animals were euthanized, and the tails of epididymis were removed to analyze sperm parameters, testis were taken for stereological assessment, reactive oxygen spices and glutathione levels, and the expression of Ocln, Gja1, Cdh2, and Itgb1.
Results: The results of sperm analysis indicated that SCCM-treated mice significantly increased sperm count and motility and reduced DNA fragmentation. In addition, histological and molecular findings showed that the volume of testicular tissue, the number of germ cells, the glutathione level, and the expression of Ocln, Gja1, Cdh2, and Itgb1 genes were significantly increased in the SCCM-treated mice.
Conclusion: Findings suggest that growth factors of SCCM stimulate the proliferation and differentiation of germ cells through paracrine effects and upregulate the blood-testis-barrier-associated genes in mice subjected to scrotal hyperthermia.
Key words: Testis, Sertoli cells, Culture media, Hyperthermia, Spermatogenesis.
References
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[8] Hu Y, Hu H, Yin L, Wang L, Luo K, Luo N, et al. Arachidonic acid impairs the function of the blood-testis barrier via triggering mitochondrial complex-ROS-P38 MAPK axis in hyperthermal Sertoli cells. Ecotoxicol Environ Saf 2023; 252: 114598.
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[10] Chen S-R, Liu Y-X. Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction 2015; 149: R159-R167.
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[12] Hajian Monfared M, Minaee B, Rastegar T, Khrazinejad E, Barbarestani M. Sertoli cell condition medium can induce germ like cells from bone marrow derived mesenchymal stem cells. Iran J Basic Med Sci 2016; 19: 1186–1192.
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[14] Afshar A, Aliaghaei A, Nazarian H, Abbaszadeh H-A, Naserzadeh P, Fathabadi FF, et al. Curcumin-loaded iron particle improvement of spermatogenesis in azoospermic mouse induced by long-term scrotal hyperthermia. Reprod Sci 2021; 28: 371–380.
[15] Ziaeipour S, Piryaei A, Aliaghaei A, Nazarian H, Naserzadeh P, Ebrahimi V, et al. Chronic scrotal hyperthermia induces azoospermia and severe damage to testicular tissue in mice. Acta Histochem 2021; 123: 151712.
[16] Ayoubi M, Naserzadeh P, Hashemi MT, Rostami MR, Tamjid E, Tavakoli MM, et al. Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis induced by lead sulfide/graphene oxide quantum dots for potential bioimaging applications. Sci Rep 2017; 7: 12896.
[17] Oliveira PF, Alves MG. Sertoli cell metabolism and spermatogenesis. Cham: Springer; 2015: 25–39.
[18] Parekh PA, Garcia TX, Hofmann M-C. Regulation of GDNF expression in Sertoli cells. Reproduction 2019; 157: R95- R107.
[19] Peng YJ, Tang XT, Shu HS, Dong W, Shao H, Zhou BO. Sertoli cells are the source of stem cell factor for spermatogenesis. Development 2023; 150: dev200706.
[20] Meroni SB, Galardo MN, Rindone G, Gorga A, Riera MF, Cigorraga SB. Molecular mechanisms and signaling pathways involved in sertoli cell proliferation. Front Endocrinol 2019; 10: 224.
[21] Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, et al. Investigation on the origin of sperm DNA fragmentation: Role of apoptosis, immaturity and oxidative stress. Mol Med 2015; 21: 109–122.
[22] Fu L, Yuen KCJ, Tint AN, Hoffman AR, Bongso AT, Lee KO. Association of decreased sperm motility and increased seminal plasma IGF-I, IGF-II, IGFBP-2, and PSA levels in infertile men. Endocrine 2021; 74: 698–706.
[23] Ghafouri-Fard S, Shoorei H, Mohaqiq M, Raza SHA, Taheri M. The role of different compounds on the integrity of blood-testis barrier: A concise review based on in vitro and in vivo studies. Gene 2021; 780: 145531.
[24] Su L, Wang Z, Xie S, Hu D, Cheng YC, Mruk DD, et al. Testin regulates the blood-testis barrier via disturbing occludin/ZO-1 association and actin organization. J Cell Physiol 2020; 235: 6127–6138.
[25] Piprek RP, Kloc M, Mizia P, Kubiak JZ. The central role of cadherins in gonad development, reproduction, and fertility. Int J Mol Sci 2020; 21: 8264.
[26] Zhang DC, Chen R, Cai YH, Wang JJ, Yin C, Zou K. Hyperactive reactive oxygen species impair function of porcine Sertoli cells via suppression of surface protein ITGB1 and connexin-43. Zool Res 2020; 41: 203–207.
[27] Yang W-R, Li B-B, Hu Y, Zhang L, Wang X-Z. Oxidative stress mediates heat-induced changes of tight junction proteins in porcine sertoli cells via inhibiting CaMKKß- AMPK pathway. Theriogenology 2020; 142: 104–113.
[28] Hofmann M-C, McBeath E. Sertoli cell-germ cell interactions within the niche: Paracrine and juxtacrine molecular communications. Front Endocrinol 2022; 13: 897062.
[29] Lv D, Zhao M, Ni J, Liu W, Ren Y, Zhu D, et al. NGF regulates sertoli cell growth and prevents LPS-induced junction protein damage via PI3K/AKT/NF?B signaling. Theriogenology 2023; 195: 138–148.
[2] Kastelic JP, Rizzoto GJBr. Thermoregulation of the testes. In: Hopper RM. Bovine reproduction. 2th Ed. US: John Wiley & Sons; 2021.
[3] Abd El-Emam MM, Ray MN, Ozono M, Kogure K. Heat stress disrupts spermatogenesis via modulation of spermspecific calcium channels in rats. J Therm Biol 2023; 112: 103465.
[4] Durairajanayagam D, Agarwal A, Ong C. Causes, effects and molecular mechanisms of testicular heat stress. Reprod Biomed Online 2015; 30: 14–27.
[5] Makela J-A, Koskenniemi JJ, Virtanen HE, Toppari J. Testis development. Endocr Rev 2019; 40: 857–905.
[6] O’Donnell L, Smith LB, Rebourcet D. Sertoli cells as key drivers of testis function. Semin Cell Dev Biol 2022; 121: 2–9.
[7] Arisha AH, Ahmed MM, Kamel MA, Attia YA, Hussein MMA. Morin ameliorates the testicular apoptosis, oxidative stress, and impact on blood–testis barrier induced by photo-extracellularly synthesized silver nanoparticles. Environ Sci Pollut Res Int 2019; 26: 28749–28762.
[8] Hu Y, Hu H, Yin L, Wang L, Luo K, Luo N, et al. Arachidonic acid impairs the function of the blood-testis barrier via triggering mitochondrial complex-ROS-P38 MAPK axis in hyperthermal Sertoli cells. Ecotoxicol Environ Saf 2023; 252: 114598.
[9] Mruk DD, Cheng CY. The mammalian blood-testis barrier: Its biology and regulation. Endocr Rev 2015; 36: 564–591.
[10] Chen S-R, Liu Y-X. Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction 2015; 149: R159-R167.
[11] Hai Y, Hou J, Liu Y, Liu Y, Yang H, Li Z, et al. The roles and regulation of Sertoli cells in fate determinations of spermatogonial stem cells and spermatogenesis. Semin Cell Dev Biol 2014; 29: 66–75.
[12] Hajian Monfared M, Minaee B, Rastegar T, Khrazinejad E, Barbarestani M. Sertoli cell condition medium can induce germ like cells from bone marrow derived mesenchymal stem cells. Iran J Basic Med Sci 2016; 19: 1186–1192.
[13] Panahi S, Karamian A, Sajadi E, Aliaghaei A, Nazarian H, Abdi Sh, et al. Sertoli cell-conditioned medium restores spermatogenesis in azoospermic mouse testis. Cell Tissue Res 2020; 379: 577–587.
[14] Afshar A, Aliaghaei A, Nazarian H, Abbaszadeh H-A, Naserzadeh P, Fathabadi FF, et al. Curcumin-loaded iron particle improvement of spermatogenesis in azoospermic mouse induced by long-term scrotal hyperthermia. Reprod Sci 2021; 28: 371–380.
[15] Ziaeipour S, Piryaei A, Aliaghaei A, Nazarian H, Naserzadeh P, Ebrahimi V, et al. Chronic scrotal hyperthermia induces azoospermia and severe damage to testicular tissue in mice. Acta Histochem 2021; 123: 151712.
[16] Ayoubi M, Naserzadeh P, Hashemi MT, Rostami MR, Tamjid E, Tavakoli MM, et al. Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis induced by lead sulfide/graphene oxide quantum dots for potential bioimaging applications. Sci Rep 2017; 7: 12896.
[17] Oliveira PF, Alves MG. Sertoli cell metabolism and spermatogenesis. Cham: Springer; 2015: 25–39.
[18] Parekh PA, Garcia TX, Hofmann M-C. Regulation of GDNF expression in Sertoli cells. Reproduction 2019; 157: R95- R107.
[19] Peng YJ, Tang XT, Shu HS, Dong W, Shao H, Zhou BO. Sertoli cells are the source of stem cell factor for spermatogenesis. Development 2023; 150: dev200706.
[20] Meroni SB, Galardo MN, Rindone G, Gorga A, Riera MF, Cigorraga SB. Molecular mechanisms and signaling pathways involved in sertoli cell proliferation. Front Endocrinol 2019; 10: 224.
[21] Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, et al. Investigation on the origin of sperm DNA fragmentation: Role of apoptosis, immaturity and oxidative stress. Mol Med 2015; 21: 109–122.
[22] Fu L, Yuen KCJ, Tint AN, Hoffman AR, Bongso AT, Lee KO. Association of decreased sperm motility and increased seminal plasma IGF-I, IGF-II, IGFBP-2, and PSA levels in infertile men. Endocrine 2021; 74: 698–706.
[23] Ghafouri-Fard S, Shoorei H, Mohaqiq M, Raza SHA, Taheri M. The role of different compounds on the integrity of blood-testis barrier: A concise review based on in vitro and in vivo studies. Gene 2021; 780: 145531.
[24] Su L, Wang Z, Xie S, Hu D, Cheng YC, Mruk DD, et al. Testin regulates the blood-testis barrier via disturbing occludin/ZO-1 association and actin organization. J Cell Physiol 2020; 235: 6127–6138.
[25] Piprek RP, Kloc M, Mizia P, Kubiak JZ. The central role of cadherins in gonad development, reproduction, and fertility. Int J Mol Sci 2020; 21: 8264.
[26] Zhang DC, Chen R, Cai YH, Wang JJ, Yin C, Zou K. Hyperactive reactive oxygen species impair function of porcine Sertoli cells via suppression of surface protein ITGB1 and connexin-43. Zool Res 2020; 41: 203–207.
[27] Yang W-R, Li B-B, Hu Y, Zhang L, Wang X-Z. Oxidative stress mediates heat-induced changes of tight junction proteins in porcine sertoli cells via inhibiting CaMKKß- AMPK pathway. Theriogenology 2020; 142: 104–113.
[28] Hofmann M-C, McBeath E. Sertoli cell-germ cell interactions within the niche: Paracrine and juxtacrine molecular communications. Front Endocrinol 2022; 13: 897062.
[29] Lv D, Zhao M, Ni J, Liu W, Ren Y, Zhu D, et al. NGF regulates sertoli cell growth and prevents LPS-induced junction protein damage via PI3K/AKT/NF?B signaling. Theriogenology 2023; 195: 138–148.