Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.
Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, PR China.
Sci Total Environ. 2020 Sep 10;734:139233. doi: 10.1016/j.scitotenv.2020.139233. Epub 2020 May 19.
Arsenic (As) poisoning and its potential reproductive functional lesions are a global environmental concern. Recent studies shown that spermiogenesis tends to be a major target process in arsenic-induced male infertility, however, the underlying mechanisms are not fully illuminated. In the present study, 32 fertility related indices including sperm motility, dynamic acrosome formation and sperm flagellum during spermiogenesis in testes were evaluated in adult male mice treated with 0, 0.2, 2, and 20 ppm AsO via drinking water for 180 consecutive days. The results showed that out of 32 indices, 11, 25, and 29 indicators were changed statistically by 0.2-, 2-, and 20- ppm AsO treatment compared to the controls (0 ppm AsO), respectively, which reveals a significant dose-dependent relationship. For details, sperm motilities were significantly decreased by 18.85%, 32.47% and 29.53% in three AsO treatment groups compared to the control group. Meanwhile, the ultra-structures of acrosome formation and sperm flagellum in testes have been altered by chronic arsenic exposure. Furthermore, arsenic decreased the mRNA expressions of 11 out of 13 genes associated with acrosome biosynthesis and 11 out of 12 genes related to flagellum formation in testes, particularly, down-regulated DPY19L2, AKAP3, AKAP4, CFAP44 and SPAG16 were further confirmed at the protein levels by western blotting. Taken together, chronic arsenic exposure declines male fertility by disorganizing dynamic acrosome and flagellum formation in testes. Especially, DPY19L2, AKAP3, AKAP4, CFAP44, and SPAG16 maybe the potential targets in this process. These results may offer not only a new insight to the mechanism of arsenic-induced male reproductive toxicity, but also provide a clue for the diagnosis and therapy of arseniasis.
砷（As）中毒及其潜在的生殖功能损伤是一个全球性的环境问题。最近的研究表明，精子发生过程容易成为砷诱导男性不育的主要靶过程，然而，其潜在机制尚未完全阐明。在本研究中，通过饮用水将成年雄性小鼠连续处理 180 天，浓度分别为 0、0.2、2 和 20ppmAsO，评估了 32 种与生育相关的指标，包括精子活力、顶体动态形成和精子鞭毛在睾丸中的精子发生过程。结果表明，在 32 个指标中，0.2、2 和 20ppmAsO 处理组与对照组（0ppmAsO）相比，有 11、25 和 29 个指标发生了统计学变化，这表明存在显著的剂量依赖性关系。具体而言，与对照组相比，三个 AsO 处理组的精子活力分别显著下降了 18.85%、32.47%和 29.53%。同时，慢性砷暴露会改变顶体形成和精子鞭毛的超微结构。此外，砷降低了 13 个与顶体生物合成相关基因中的 11 个和 12 个与鞭毛形成相关基因中的 11 个在睾丸中的 mRNA 表达，特别是 DPY19L2、AKAP3、AKAP4、CFAP44 和 SPAG16 的表达下调，通过蛋白质印迹进一步证实。总之，慢性砷暴露通过扰乱睾丸中动态顶体和鞭毛的形成，降低了雄性生育能力。特别是，DPY19L2、AKAP3、AKAP4、CFAP44 和 SPAG16 可能是这个过程中的潜在靶点。这些结果不仅为砷诱导男性生殖毒性的机制提供了新的见解，也为砷中毒的诊断和治疗提供了线索。
