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经口给予小鼠氧化锌纳米粒子后生殖器官功能障碍和基因表达。

Reproductive organ dysfunction and gene expression after orally administration of ZnO nanoparticles in murine.

机构信息

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.

R&D Center, Zystein, LLC, Fayetteville, Arkansas, USA.

出版信息

Environ Toxicol. 2021 Apr;36(4):550-561. doi: 10.1002/tox.23060. Epub 2020 Nov 25.

DOI:10.1002/tox.23060
PMID:33236829
Abstract

ZnO nanoparticles (NPs) are among the most manufactured nanoparticles in the consumer products, industries, and researches. An increasing body of evidence indicated that ZnO NPs show toxicological effects in vivo. Sex differences in the toxicity of ZnO NPs are not clear, thus the aim of this study was to investigate the effects of ZnO NPs on the female and male reproductive organs (uterus, ovary and testes). ZnO NPs were orally administered to female and male mice at dosages level of 0 and 100 mg/kg body weight. The biological material was sampled 3 days after tube feeding. The results demonstrated that Zinc contents were accumulated in the reproductive organs of treated mice. Furthermore, ZnO NPs administration induced significant decrease in the testes weight, an imbalance of hematological and serum biochemical parameters in male mice. The histopathological examinations showed that structural disorder and the appearance of cell apoptosis and death in the ZnO NPs-exposed mice. Additionally, the RT-qPCR data indicated ZnO NPs can activate mitochondrial-mediated signaling pathway and induce caspase depend damage that ultimately injured the uterus. In the ovary, ZnO NPs induce cell apoptosis in Shh pathway activated ovary cells, and affect the synthesis of steroidogenesis. In the testes, ZnO NPs effectively changed the expression level of genes related to oxidant stress, detox/metabolic process, and apoptosis. It was found that ZnO NPs caused more serious reproductive toxicity in the male mice than female mice. Overall, these findings indicated that ZnO NPs could induce exposure-related risks to reproductive health, especially in those who are at the occupational level.

摘要

氧化锌纳米粒子(NPs)是在消费品、工业和研究中制造最多的纳米粒子之一。越来越多的证据表明,氧化锌 NPs 在体内表现出毒理学效应。氧化锌 NPs 的毒性在性别上的差异尚不清楚,因此本研究旨在研究氧化锌 NPs 对雌性和雄性生殖器官(子宫、卵巢和睾丸)的影响。将氧化锌 NPs 以 0 和 100mg/kg 体重的剂量水平经口给予雌性和雄性小鼠。在管饲后 3 天采集生物材料。结果表明,锌含量在处理小鼠的生殖器官中积累。此外,氧化锌 NPs 给药导致雄性小鼠睾丸重量显著下降,血液学和血清生化参数失衡。组织病理学检查显示,暴露于 ZnO NPs 的小鼠出现结构紊乱和细胞凋亡和死亡的外观。此外,RT-qPCR 数据表明,氧化锌 NPs 可以激活线粒体介导的信号通路,并诱导依赖半胱天冬酶的损伤,最终损伤子宫。在卵巢中,氧化锌 NPs 诱导 Shh 通路激活的卵巢细胞凋亡,并影响类固醇生成的合成。在睾丸中,氧化锌 NPs 有效改变了与氧化应激、解毒/代谢过程和细胞凋亡相关的基因的表达水平。研究发现,氧化锌 NPs 对雄性小鼠的生殖毒性比雌性小鼠更严重。总的来说,这些发现表明,氧化锌 NPs 可能会对生殖健康造成与暴露相关的风险,特别是在职业暴露水平的人群中。

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