Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death.

Tytuł:: Mebendazole-Induced Blood-Testis Barrier Injury in Mice Testes by Disrupting Microtubules in Addition to Triggering Programmed Cell Death.
Autorzy:: Huang M; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Wang C; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Yao Y; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Li H; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Yao Y; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Zhu Y; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Cui Y; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Yuan Y; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Sha J; Department of Histology and Embryology, Nanjing Medical University, Nanjing 210000, China.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2022 Apr 11; Vol. 23 (8). Date of Electronic Publication: 2022 Apr 11.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Blood-Testis Barrier*/metabolism
Mebendazole*/pharmacology
Animals ; Apoptosis ; Caspase 3/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microtubules ; Sertoli Cells/metabolism ; Testis
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Grant Information:: 2017YFA0103803 and 2021YFC2700200 National Key R&D Program; 92068109 National Natural Science Foundation of China
Contributed Indexing:: Keywords: Sertoli; apoptosis; blood-testis barrier; mebendazole; tubulin
Substance Nomenclature:: 81G6I5V05I (Mebendazole)
EC 3.4.22.- (Caspase 3)
Entry Date(s):: Date Created: 20220423 Date Completed: 20220426 Latest Revision: 20220716
Update Code:: 20240105
PubMed Central ID:: PMC9029725
DOI:: 10.3390/ijms23084220
PMID:: 35457043
: Czasopismo naukowe

Pełny tekst

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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