Arsenic interferes with spermatogenesis involving Rictor/mTORC2-mediated blood-testis barrier disruption in mice.

Autor: Li X; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China., Wang W; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China., Hou Y; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China; Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China., Li G; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China; Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China., Yi H; School of Life Science, Shanxi University, Taiyuan 030006, China., Cui S; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China; Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China., Zhang J; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China., He X; Taiyuan Hospital of Integrated Traditional Chinese and Western Medicine, Taiyuan 030003, China., Zhao H; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China., Yang Z; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China., Qiu Y; Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China. Electronic address: ylqiu@sxmu.edu.cn., Liu Z; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China. Electronic address: zhizhenliu2013@163.com., Xie J; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, China, Shanxi Medical University, Taiyuan 030001, China. Electronic address: junxie@sxmu.edu.cn.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2023 Jun 01; Vol. 257, pp. 114914. Date of Electronic Publication: 2023 Apr 19.
DOI: 10.1016/j.ecoenv.2023.114914
Abstrakt: Ingestion of arsenic interferes with spermatogenesis and increases the risk of male infertility, but the underlying mechanism remines unclear. In this study, we investigated spermatogenic injury with a focus on blood-testis barrier (BTB) disruption by administrating 5 mg/L and 15 mg/L arsenic orally to adult male mice for 60 d. Our results showed that arsenic exposure reduced sperm quality, altered testicular architecture, and impaired Sertoli cell junctions at the BTB. Analysis of BTB junctional proteins revealed that arsenic intake downregulated Claudin-11 expression and increased protein levels of β-catenin, N-cadherin, and Connexin-43. Aberrant localization of these membrane proteins was also observed in arsenic-treated mice. Meanwhile, arsenic exposure altered the components of Rictor/mTORC2 pathway in mouse testis, including inhibition of Rictor expression, reduced phosphorylation of protein kinase Cα (PKCα) and protein kinase B (PKB), and elevated matrix metalloproteinase-9 (MMP-9) levels. Furthermore, arsenic also induced testicular lipid peroxidative damage, inhibited antioxidant enzyme (T-SOD) activity, and caused glutathione (GSH) depletion. Our findings suggest that disruption of BTB integrity is one of the main factors responsible for the decline in sperm quality caused by arsenic. PKCα-mediated rearrangement of actin filaments and PKB/MMP-9-increased barrier permeability jointly contribute to arsenic-induced BTB disruption.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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