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自噬和凋亡介导的纳米铜诱导的睾丸损伤。

Autophagy and apoptosis mediated nano-copper-induced testicular damage.

机构信息

College of Veterinary Medicine, Sichuan Agricultural University, 211 Huimin Road, Chengdu 611130, Sichuan, China.

College of Veterinary Medicine, Sichuan Agricultural University, 211 Huimin Road, Chengdu 611130, Sichuan, China; National Ethnic Affairs Commission Key Open Laboratory of Traditional Chinese Veterinary Medicine, Tongren Polytechnic College, Tongren 554300, Guizhou, China.

出版信息

Ecotoxicol Environ Saf. 2022 Jan 1;229:113039. doi: 10.1016/j.ecoenv.2021.113039. Epub 2021 Dec 15.

DOI:10.1016/j.ecoenv.2021.113039
PMID:34922170
Abstract

Nano-copper has been increasingly employed in various products. In previous studies, we showed that nano-copper caused damage in the rat testis, but it remains unclear whether the toxic reaction can affect the reproductive function. In this study, following 28 d of exposure to nano-copper at a dose of 44, 88, and 175 mg/kg/day, there was a decrease in sperm quality, fructose content, and the secretion of sex hormones. Nano-copper also increased the level of oxidative stress, sperm malformation rate, and induced abnormal structural changes in testicular tissue. Moreover, Nano-copper upregulated the expression of apoptosis-related protein Bax and autophagy-related protein Beclin, and downregulated the expression of Bcl2 and p62. Furthermore, nano-copper (175 mg/kg) downregulated the protein expression of AMPK, p-AKT, mTOR, p-mTOR, p-4E-BP1, p70S6K, and p-p70S6K, and upregulated the protein expression of p-AMPK. Therefore, nano-copper induced damage in testicular tissues and spermatogenesis is highly related to cell apoptosis and autophagy by regulating the Akt/mTOR signaling pathway. In summary, excess exposure to nano-copper may induce testicular apoptosis and autophagy through AKT/mTOR signaling pathways, and damage the reproductive system in adult males, which is associated with oxidative stress in the testes.

摘要

纳米铜在各种产品中的应用越来越广泛。在之前的研究中,我们已经表明纳米铜会对老鼠的睾丸造成损伤,但目前尚不清楚这种毒性反应是否会影响生殖功能。在这项研究中,大鼠在每天摄入 44、88 和 175mg/kg 剂量的纳米铜 28 天后,精子质量、果糖含量和性激素的分泌均下降。纳米铜还增加了氧化应激水平、精子畸形率,并导致睾丸组织出现异常结构变化。此外,纳米铜上调了凋亡相关蛋白 Bax 和自噬相关蛋白 Beclin 的表达,下调了 Bcl2 和 p62 的表达。此外,纳米铜(175mg/kg)下调了 AMPK、p-AKT、mTOR、p-mTOR、p-4E-BP1、p70S6K 和 p-p70S6K 的蛋白表达,上调了 p-AMPK 的蛋白表达。因此,纳米铜诱导睾丸组织和精子发生损伤与细胞凋亡和自噬密切相关,通过调节 Akt/mTOR 信号通路。总之,过量暴露于纳米铜可能会通过 Akt/mTOR 信号通路诱导睾丸细胞凋亡和自噬,损害成年雄性的生殖系统,这与睾丸中的氧化应激有关。

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