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...

Full description

Bibliographic Details
Main Authors: Mingqian Huang, Chang Wang, Ying Yao, Huiling Li, Yejin Yao, Yunfei Zhu, Yiqiang Cui, Yan Yuan, Jiahao Sha
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/8/4220
_version_ 1797434563099623424
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.
first_indexed 2024-03-09T10:34:06Z
format Article
id doaj.art-6915a1d93c3b413aab9dc0ad130f3b08
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T10:34:06Z
publishDate 2022-04-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
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
work_keys_str_mv AT mingqianhuang mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT changwang mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT yingyao mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT huilingli mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT yejinyao mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT yunfeizhu mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT yiqiangcui mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT yanyuan mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath
AT jiahaosha mebendazoleinducedbloodtestisbarrierinjuryinmicetestesbydisruptingmicrotubulesinadditiontotriggeringprogrammedcelldeath