Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, 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, China.
Chemosphere. 2020 Jan;238:124650. doi: 10.1016/j.chemosphere.2019.124650. Epub 2019 Aug 23.
Arsenic (As) has become a major problem in maintaining the environment and human health due to its wide application in the production of agriculture and industry. Many studies indicate that As can affect spermatogenesis process and lower sperm quality. However, the undergoing molecular mechanism is unclear. For this, forty-eight 8-week old adult male mice were divided into four groups of twelve each, which were administrated to 0, 0.2, 2, 20 ppm AsO in their drinking water respectively for six months. The results showed that As treatment reduced sperm counts and increased the sperm malformation ratio of mice. Interestingly, both the amounts of round and elongated spermatids, and the ratios of spermatids elongation were decreased significantly by As exposure. Furthermore, the structure of Chromatoid Body (CB) which presents a typical nebulous shape in round spermatids after spermatogenesis arrested, and the mRNA expression levels of gene TDRD1, TDRD6 and TDRD7 related to CB were changed by arsenic. Again, the mRNA and protein expression levels of the markers DDX25 and CRM1 in haploid periods of spermatogenesis and the associated proteins HMG2, PGK2, and H4 with DDX25 regulation were declined significantly with As treatment. Taken together; it reveals that As interferes with spermatogenesis by disorganizing the elongation of spermatids. H4, HMG2 and PGK2 are regulated by DDX25 which interacts with CRM1 and may play a vital role in spermatogenesis disorder induced by As exposure, which maybe provides one of the underlying mechanisms for As-induced male reproductive toxicity.
砷(As)由于其在农业和工业生产中的广泛应用,已成为维护环境和人类健康的主要问题。许多研究表明,砷会影响精子发生过程并降低精子质量。然而,其作用的分子机制尚不清楚。为此,将 48 只 8 周龄成年雄性小鼠分为 4 组,每组 12 只,分别给予 0、0.2、2、20ppm 的砷在饮用水中,连续处理 6 个月。结果表明,砷处理降低了精子计数并增加了小鼠的精子畸形率。有趣的是,砷暴露显著降低了圆和长形精母细胞的数量以及精母细胞伸长的比例。此外,砷暴露改变了染色质体(CB)的结构,CB 在精子发生停滞后呈现典型的云雾状形态,与 CB 相关的 TDRD1、TDRD6 和 TDRD7 的基因表达水平也发生了变化。再次,在单倍体时期与精子发生相关的标志物 DDX25 和 CRM1 的 mRNA 和蛋白表达水平以及与 DDX25 调节相关的 HMG2、PGK2 和 H4 的蛋白表达水平均随砷处理而显著下降。总之,结果揭示了砷通过打乱精子的伸长来干扰精子发生。H4、HMG2 和 PGK2 受 DDX25 调节,DDX25 与 CRM1 相互作用,可能在砷暴露引起的精子发生障碍中发挥重要作用,这为砷引起的雄性生殖毒性提供了潜在机制之一。