ZnO Nanoparticles Induced Male Reproductive Toxicity Based on the Effects on the Endoplasmic Reticulum Stress Signaling Pathway

Abstract

Yizhou Tang,1 Bolu Chen,1 Wuding Hong,1 Ling Chen,1,2 Liyang Yao,1 Yu Zhao,1 Zoraida P Aguilar,3 Hengyi Xu1 1State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, People’s Republic of China; 2The Second Affiliated Hospital of Nanchang University, Nanchang 330000, People’s Republic of China; 3Zystein, LLC., Fayetteville, AR 72704, USACorrespondence: Hengyi XuState Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, People’s Republic of ChinaTel [phone] ext 9520Fax [phone]Email [email protected]: 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.Keywords: zinc oxide nanoparticles, male reproductive toxicity, endoplasmic reticulum stress

Keywords

• zinc oxide nanoparticles
• male reproductive toxicity
• endoplasmic reticulum stress