Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death
Mebendazole (MBZ) is a synthetic benzimidazole known for its antiparasitic properties. In recent years, growing evidence showed that MBZ was also used as an anti-tumor agent. However, whether (and to what extent) this drug treatment affected the male reproductive system was not well-understood. In t...
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2022-04-01
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author | Mingqian Huang Chang Wang Ying Yao Huiling Li Yejin Yao Yunfei Zhu Yiqiang Cui Yan Yuan Jiahao Sha |
author_facet | Mingqian Huang Chang Wang Ying Yao Huiling Li Yejin Yao Yunfei Zhu Yiqiang Cui Yan Yuan Jiahao Sha |
author_sort | Mingqian Huang |
collection | DOAJ |
description | Mebendazole (MBZ) is a synthetic benzimidazole known for its antiparasitic properties. In recent years, growing evidence showed that MBZ was also used as an anti-tumor agent. However, whether (and to what extent) this drug treatment affected the male reproductive system was not well-understood. In this study, male C57BL/6 mice were injected with 40 mg/kg/day of MBZ. The treatment was for 3 and 7 days. Our results showed that the injected mice exhibited an abnormal spermatogenic phase with a significant decrease in sperm. We further detected microtubule disruption and transient functional destruction of the blood–testes barrier (BTB) in the MBZ-injected mice testes (BTB). Our data confirmed that MBZ suppressed the expression of the BTB junction-associated proteins and disrupted the Sertoli cells’ function in vivo. Moreover, MBZ-treated mice demonstrated an aberrant caspase-3 signalling pathway, which resulted in the apoptosis of the germ cells. Here, we present our data, indicating that MBZ impairs BTB by reducing the expression of the microtubules’ and BTB junction-associated proteins. The last leads to activating the caspase-3 pathway, which triggers extensive germ cell apoptosis. |
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language | English |
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publishDate | 2022-04-01 |
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spelling | doaj.art-6915a1d93c3b413aab9dc0ad130f3b082023-12-01T21:03:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238422010.3390/ijms23084220Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell DeathMingqian Huang0Chang Wang1Ying Yao2Huiling Li3Yejin Yao4Yunfei Zhu5Yiqiang Cui6Yan Yuan7Jiahao Sha8Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaDepartment of Histology and Embryology, Nanjing Medical University, Nanjing 210000, ChinaMebendazole (MBZ) is a synthetic benzimidazole known for its antiparasitic properties. In recent years, growing evidence showed that MBZ was also used as an anti-tumor agent. However, whether (and to what extent) this drug treatment affected the male reproductive system was not well-understood. In this study, male C57BL/6 mice were injected with 40 mg/kg/day of MBZ. The treatment was for 3 and 7 days. Our results showed that the injected mice exhibited an abnormal spermatogenic phase with a significant decrease in sperm. We further detected microtubule disruption and transient functional destruction of the blood–testes barrier (BTB) in the MBZ-injected mice testes (BTB). Our data confirmed that MBZ suppressed the expression of the BTB junction-associated proteins and disrupted the Sertoli cells’ function in vivo. Moreover, MBZ-treated mice demonstrated an aberrant caspase-3 signalling pathway, which resulted in the apoptosis of the germ cells. Here, we present our data, indicating that MBZ impairs BTB by reducing the expression of the microtubules’ and BTB junction-associated proteins. The last leads to activating the caspase-3 pathway, which triggers extensive germ cell apoptosis.https://www.mdpi.com/1422-0067/23/8/4220blood-testis barrierSertolimebendazoletubulinapoptosis |
spellingShingle | Mingqian Huang Chang Wang Ying Yao Huiling Li Yejin Yao Yunfei Zhu Yiqiang Cui Yan Yuan Jiahao Sha Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death International Journal of Molecular Sciences blood-testis barrier Sertoli mebendazole tubulin apoptosis |
title | Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death |
title_full | Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death |
title_fullStr | Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death |
title_full_unstemmed | Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death |
title_short | Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death |
title_sort | mebendazole induced blood testis barrier injury in mice testes by disrupting microtubules in addition to triggering programmed cell death |
topic | blood-testis barrier Sertoli mebendazole tubulin apoptosis |
url | https://www.mdpi.com/1422-0067/23/8/4220 |
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