ZnO Nanoparticles Induced Male Reproductive Toxicity Based on the Effects on the Endoplasmic Reticulum Stress Signaling Pathway
ZnO Nanoparticles Induced Male Reproductive Toxicity Based on the Effects on the Endoplasmic Reticulum Stress Signaling Pathway
复制标题
氧化锌纳米颗粒对内质网应激信号通路的影响诱导男性生殖毒性
DOI：
10.2147/ijn.s223318
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发表时间：
2019
影响因子：
8
通讯作者：
Xu Hengyi
中科院分区：
文献类型：
--
作者：
Tang Yizhou;Chen Bolu;Hong Wuding;Chen Ling;Yao Liyang;Zhao Yu;Aguilar Zoraida P.;Xu Hengyi
目的本研究旨在评价ZnO NPs对男性生殖系统的不良影响并探讨其可能的机制。方法 在这项研究中，研究了成年雄性小鼠口服 50、150 和 450 mg/kg 氧化锌纳米粒子 (ZnO NPs) 的效果，为期 14 天。结果结果表明，随着ZnO NPs剂量的增加，附睾精子数量和血清中睾酮浓度降低。观察到睾丸组织病理学病变，如生殖细胞脱离、萎缩和空泡化。结果表明，增加ZnO NPs剂量会相应上调与ER应激相关的IRE1α、XBP1s、BIP和CHOP基因（P<0.05）。这些观察结果表明，ZnO NPs可能通过ER应激以剂量依赖性方式对男性生殖系统产生不利影响。所有治疗组中caspase-3的表达均显着增加（P<0.001），这反映了细胞凋亡可能被激活。此外，睾酮合成中的关键基因StAR也显着下调（P<0.05）。当将 ER 应激抑制剂 salubrinal 给予 450 mg/kg ZnO NPs 治疗组时，未观察到生精管损伤以及支持细胞和 Leydig 细胞空泡化。此外，在随后的 salubrinal 治疗后，血清中的睾酮水平与对照组相似。结论 ZnO NP对雄性小鼠的生殖毒性可能是通过细胞凋亡和ER应激信号通路发生的。
Purpose The aim of this study was to evaluate the adverse effects of ZnO NPs on male reproductive system and explore the possible mechanism. Methods In this study, the effect of oral administration of 50, 150 and 450 mg/kg zinc oxide nanoparticles (ZnO NPs) in adult male mice was studied over a 14-day period. Results The results showed that the number of sperms in the epididymis and the concentration of testosterone in serum were decreased with an increased dose of ZnO NPs. Testicular histopathological lesions like detachment, atrophy and vacuolization of germ cells were observed. The results showed that increased dosage of ZnO NPs correspondingly up-regulated the IRE1α, XBP1s, BIP, and CHOP (P<0.05) which are genes related to ER stress. These observations indicated that ZnO NPs had adverse effects on the male reproductive system in a dose-dependent manner possibly through ER stress. The expression of caspase-3 was significantly increased in all the treated groups (P<0.001), which reflected the possible activation of apoptosis. Additionally, there was significant down-regulation of the gene StAR (P<0.05), a key player in testosterone synthesis. When an ER-stress inhibitor salubrinal was administered to the 450 mg/kg ZnO NPs treatment group, the damages to the seminiferous tube and vacuolization of Sertoli and Leydig cells were not observed. Furthermore, the testosterone levels in the serum were similar to the control group after the subsequent salubrinal treatment. Conclusion It may be inferred that the ZnO NP's reproductive toxicity in male mice occurred via apoptosis and ER-stress signaling pathway.