Yang Jing, Hu Shifu, Rao Meng, Hu Lixia, Lei Hui, Wu Yanqing, Wang Yingying, Ke Dandan, Xia Wei, Zhu Chang-Hong
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei.
Department of Histology and Embryology, Preclinical Medicine College, Xinxiang Medical University, Henan Province, Xinxiang.
Int J Nanomedicine. 2017 Aug 18;12:5959-5971. doi: 10.2147/IJN.S139215. eCollection 2017.
Numerous studies have reported the accumulation of copper nanoparticles (Cu NPs) in organs and the corresponding damage, although whether Cu NPs can be translocated to the ovaries and their ovarian toxicity are still unknown. In this study, three groups of female rats were injected with 3.12, 6.25, or 12.5 mg/kg Cu NPs for 14 consecutive days. The pathological changes, hormone levels, apoptosis and apoptotic proteins, oxidative stress, and gene expression characteristics in the ovaries were then investigated. The results demonstrated that the Cu NPs exhibited obvious accumulation in the rat ovaries, leading to ovarian injury, an imbalance of sex hormones, and ovarian cell apoptosis. Cu NP exposure activated caspase 3, caspase 8, caspase 9, and tBid, decreased the protein levels of Bcl-2, increased the expression levels of the proteins Bax and cytochrome , and promoted malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) reduction. Furthermore, gene microarray analysis showed that Cu NPs (12.5 mg/kg/d) caused 321 differentially expressed genes. Of these, 180 and 141 genes were upregulated and downregulated, respectively. , , , and were involved in steroid and hormone metabolism, whereas and were associated with apoptosis. Overall, these findings provide strong evidence that Cu NPs trigger both intrinsic and extrinsic apoptotic pathways and regulate key ovarian genes in oxidative stress-mediated ovarian dysfunction.
众多研究报告了铜纳米颗粒（Cu NPs）在器官中的蓄积及相应损害，尽管Cu NPs是否能转运至卵巢及其卵巢毒性仍不清楚。在本研究中，三组雌性大鼠连续14天注射3.12、6.25或12.5 mg/kg的Cu NPs。随后研究了卵巢中的病理变化、激素水平、细胞凋亡及凋亡蛋白、氧化应激和基因表达特征。结果表明，Cu NPs在大鼠卵巢中表现出明显蓄积，导致卵巢损伤、性激素失衡和卵巢细胞凋亡。暴露于Cu NPs激活了半胱天冬酶3、半胱天冬酶8、半胱天冬酶9和截短型Bid，降低了Bcl-2蛋白水平，增加了Bax和细胞色素蛋白的表达水平，并促进了丙二醛（MDA）蓄积和超氧化物歧化酶（SOD）减少。此外，基因芯片分析表明，Cu NPs（12.5 mg/kg/d）导致321个差异表达基因。其中，180个和141个基因分别上调和下调。 、 、 和 参与类固醇和激素代谢，而 和 与细胞凋亡相关。总体而言，这些发现提供了有力证据，证明Cu NPs触发内在和外在凋亡途径，并在氧化应激介导的卵巢功能障碍中调节关键卵巢基因。
