PurposeThe aim of this study was to evaluate the adverse effects of ZnO NPs on male reproductive system and explore the possible mechanism.MethodsIn 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.ResultsThe 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.ConclusionIt may be inferred that the ZnO NP's reproductive toxicity in male mice occurred via apoptosis and ER-stress signaling pathway.
ZnO NPs have been assessed to show adverse effects on reproductive organs, but the molecular mechanisms of reproductive toxicity have not been sufficiently studied. In this research, the dosage effects from the oral exposure of ZnO NPs (30 nm) to pregnant mice in gestation day 10.5 to 17.5 was analyzed. Pregnant mice exposed to ZnO NPs induced dam injury, mice fetal growth restriction, and the fetus number decreased. The pathological evaluation showed that ZnO NPs exposure caused placental spongiotrophoblast area decease and structural damage. The RT-qPCR and immunocytochemistry data indicated that ZnO NPs could induce placenta oxide stress, endoplasmic reticulum stress responses, apoptosis, and altered placental function. These findings indicated that ZnO NPs could induce dam injury and fetal growth restriction. Reproductive toxicity of ZnO NPs may be due to placental injury and function alteration caused by apoptosis, oxide stress, and endoplasmic reticulum stress after ZnO NPs exposure.
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