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 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.
Ecotoxicol Environ Saf. 2023 Jun 1;257:114914. doi: 10.1016/j.ecoenv.2023.114914. Epub 2023 Apr 19.
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.
砷的摄入会干扰精子发生，增加男性不育的风险，但潜在的机制尚不清楚。在这项研究中，我们通过给成年雄性小鼠口服 5mg/L 和 15mg/L 的砷，研究了砷暴露对生精的损伤，重点关注血睾屏障（BTB）的破坏。结果显示，砷暴露降低了精子质量，改变了睾丸结构，并损害了 BTB 处的支持细胞连接。对 BTB 连接蛋白的分析表明，砷摄入下调 Claudin-11 的表达，并增加β-连环蛋白、N-钙黏蛋白和连接蛋白-43 的蛋白水平。在砷处理的小鼠中也观察到这些膜蛋白的异常定位。同时，砷暴露改变了小鼠睾丸中 Rictor/mTORC2 通路的组成，包括抑制 Rictor 的表达、减少蛋白激酶 Cα（PKCα）和蛋白激酶 B（PKB）的磷酸化，以及升高基质金属蛋白酶-9（MMP-9）水平。此外，砷还诱导睾丸脂质过氧化损伤，抑制抗氧化酶（T-SOD）活性，导致谷胱甘肽（GSH）耗竭。我们的研究结果表明，BTB 完整性的破坏是砷导致精子质量下降的主要因素之一。PKCα 介导的肌动蛋白丝重排和 PKB/MMP-9 增加的屏障通透性共同导致砷诱导的 BTB 破坏。
