College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China; Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China.
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.
Ecotoxicol Environ Saf. 2023 Dec;268:115679. doi: 10.1016/j.ecoenv.2023.115679. Epub 2023 Nov 16.
Nickel (Ni) is the most important environmental pollution in the world. Ni has been confirmed to have multi-organ toxicology and carcinogenicity. Recently, Ni also can impair the male reproductive system, however, its precious mechanism still has not been clarified. The current work found that nickel chloride (NiCl) induced histopathological lesions in testis. And, the Johnsen's score, seminiferous tubule diameter, and spermatogenic epithelium thickness were decreased in NiCl-treated mice. The number of spermatogonium, primary spermatocyte, and round spermatid also were significantly reduced after Ni treatment. Next the potential molecular mechanism was measured. NiCl treatment elevated ROS production in the testis. Additionally, NiCl was found to induce apoptosis with features including up-regulation of Bax, cleaved-caspase-3, cleaved-caspase-8, caspase-9, and caspase-12, while down-regulation of Bcl-2 expression. In the meantime, the marker protein of DNA damage γ-H2AX was significantly increased in NiCl-primed mice testis. To clarify effects of reactive oxygen species (ROS) in apoptosis and DNA damage induced by NiCl, NiCl was used to co-treat antioxidant NAC (N-Acetyl-L-cysteine). NAC weakened ROS production induced by NiCl, and played an inhibition role in apoptosis and DNA damage. Moreover, co-treatment using NiCl and NAC group also eliminated spermatogenesis disorders. In summary, research results reveal the relations of spermatogenesis disorder induced by NiCl with apoptosis and DNA damage mediated by ROS and apoptosis in the testis.
镍（Ni）是世界上最重要的环境污染因素之一。已有研究证实镍具有多器官毒性和致癌性。最近，镍还可能损害男性生殖系统，但其中的具体机制尚不清楚。本研究发现氯化镍（NiCl）可诱导睾丸组织发生组织病理学损伤，且 NiCl 处理可降低小鼠的约翰森评分、曲细精管直径和生精上皮厚度，生精细胞、精原细胞和圆形精子细胞的数量也显著减少。进一步检测潜在的分子机制发现，NiCl 可增加睾丸组织中的活性氧（ROS）生成，诱导细胞凋亡，表现为 Bax、cleaved-caspase-3、cleaved-caspase-8、caspase-9 和 caspase-12 表达上调，Bcl-2 表达下调。同时，NiCl 处理组小鼠睾丸中的 DNA 损伤标志物 γ-H2AX 显著增加。为了阐明 NiCl 诱导的 ROS 对细胞凋亡和 DNA 损伤的影响，本研究使用抗氧化剂 NAC（N-乙酰-L-半胱氨酸）共同处理 NiCl。NAC 可减弱 NiCl 诱导的 ROS 生成，并在细胞凋亡和 DNA 损伤中发挥抑制作用。此外，NiCl 和 NAC 共同处理组还消除了精子发生障碍。综上，本研究结果揭示了 NiCl 诱导的精子发生障碍与 ROS 介导的凋亡和 DNA 损伤以及睾丸中的细胞凋亡之间的关系。
