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; Author affiliations: National Ethnic Affairs Commission Key Open Laboratory of Traditional Chinese Veterinary Medicine, Tongren Polytechnic College, Tongren 554300, Guizhou, China.
Ecotoxicol Environ Saf. 2021 Sep 1;220:112364. doi: 10.1016/j.ecoenv.2021.112364. Epub 2021 May 26.
Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl.2 HO increased the accumulation of copper. Besides, nano-Cu and CuCl.2 HO disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl.2 HO. In addition, exposure to nano-Cu (180 mg/kg) and CuCl.2 HO induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl.2 HO upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl.2 HO downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
纳米铜（nano-Cu）由于其独特的物理化学特性和生物活性，广泛应用于医药领域和动物饲料添加剂。在我们之前的研究中，发现纳米铜会阻碍胎儿发育；然而，纳米铜的毒性及其对胎盘功能的影响尚未阐明。因此，我们使用大鼠胎盘研究了纳米铜的毒性作用。从妊娠第 3 天（GD 3）到 GD 18，给怀孕的 Sprague-Dawley 大鼠口服不同的铜源。我们发现纳米铜（180mg/kg）和 CuCl.2·2H2O 增加了铜的积累。此外，纳米铜和 CuCl.2·2H2O 破坏了胎盘形态并诱导氧化应激。微铜（micro-Cu）在胎盘上引起类似的毒性，但作用弱于纳米铜和 CuCl.2·2H2O。此外，暴露于纳米铜（180mg/kg）和 CuCl.2·2H2O 会引起大鼠胎盘炎症。此外，纳米铜、微铜和 CuCl.2·2H2O 上调了自噬相关蛋白 Beclin-1 和 LC3 II/LC3 I 的表达，并下调了 p62 的表达。此外，纳米铜、微铜和 CuCl.2·2H2O 下调了大鼠胎盘 PI3K、p-AKT/AKT 和 p-mTOR/mTOR 的蛋白表达，而 p-AMPK/AMPK 的蛋白表达上调。总之，我们的数据表明，产前暴露于纳米铜通过 PI3K/AKT/mTOR 和 AMPK/mTOR 途径诱导自噬，与大鼠胎盘的氧化应激和炎症有关。
