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

Xiujuan Li; Wenting Wang; Yue Hou; Gexuan Li; Huilan Yi; Shuo Cui; Juan Zhang; Xiaohong He; Hong Zhao; Zeyu Yang; Yulan Qiu; Zhizhen Liu; Jun Xie

Ecotoxicology and Environmental Safety (Jun 2023)

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

Xiujuan Li,
Wenting Wang,
Yue Hou,
Gexuan Li,
Huilan Yi,
Shuo Cui,
Juan Zhang,
Xiaohong He,
Hong Zhao,
Zeyu Yang,
Yulan Qiu,
Zhizhen Liu,
Jun Xie

Affiliations

Xiujuan Li: 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
Wenting Wang: 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
Yue Hou: 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
Gexuan Li: 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
Huilan Yi: School of Life Science, Shanxi University, Taiyuan 030006, China
Shuo Cui: 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
Juan Zhang: 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
Xiaohong He: Taiyuan Hospital of Integrated Traditional Chinese and Western Medicine, Taiyuan 030003, China
Hong Zhao: 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
Zeyu Yang: 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
Yulan Qiu: Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China; Corresponding authors.
Zhizhen Liu: 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; Corresponding authors.
Jun Xie: 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; Corresponding authors.

Journal volume & issue: Vol. 257
p. 114914

Abstract

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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.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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