Gold nanoparticles cause size-dependent inhibition of embryonic development during murine pregnancy
Gold nanoparticles (Au NPs) have been widely utilized in biomedical applications owing to their attractive features and biocompatibility, which greatly increase the risk of humans’ being exposed to Au NPs, including pregnant women. In contrast to mature cells, embryos are more susceptible to outside disruptive stimuli. Nonetheless, a possible inhibitory effect of nanomaterials on embryonic development is usually ignored as long as the NPs do not have significant cytotoxic effects. According to our results, a minimal “nontoxic” concentration of Au NPs during early pregnancy can have lethal inhibitory effects on embryos in vivo and in vitro. We conducted important experiments on the influence of Au NPs on embryonic development and found that Au NPs can disturb embryonic development in a size- and concentration-dependent manner. Au NPs of 15 nm in diameter downregulated the expression pattern of distinct germ layer markers both at mRNA and protein levels; this action prevented differentiation of all three embryonic germ layers. Consequently, fetal resorption was observed. Our work reveals the impact of Au NPs on embryonic development and will provide an important guidance and serve as a reference for biomedical applications of Au NPs with minimal side effects.
Keywordsgold nanoparticles embryonic development fetal resorption differentiation
Unable to display preview. Download preview PDF.
This work was supported by the National Natural Science Foundation of China (No. 31600808), the Beijing Natural Science Foundation (No. 7164316). This work was supported in part by Chinese Natural Science Foundation key projects (Nos. 31630027 and 31430031). The authors also appreciate the support of the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDA09030301).
- Lin, C. A. J.; Yang, T. Y.; Lee, C. H.; Huang, S. H.; Sperling, R. A.; Zanella, M.; Li, J. K.; Shen, J. L.; Wang, H. H.; Yeh, H.-I. et al. Synthesis, characterization, and bioconjugation of fluor-escent gold nanoclusters toward biological labeling applications. ACS Nano 2009, 3, 395–401.CrossRefGoogle Scholar
- Hougaard, K. S.; Jackson, P.; Jensen, K. A.; Sloth, J. J.; Löschner, K.; Larsen, E. H.; Birkedal, R. K.; Vibenholt, A.; Boisen, A. M. Z.; Wallin, H. et al. Effects of prenatal exposure to surface-coated nanosized titanium dioxide (Uv-Titan). A study in mice. Part. Fibre Toxicol. 2010, 7, 16.CrossRefGoogle Scholar
- Lim, J. H.; Kim, S. H.; Shin, I. S.; Park, N. H.; Moon, C.; Kang, S. S.; Kim, S. H.; Park, S. C.; Kim, J. C. Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats. Birth Defects Res. Part B: Dev. Reprod. Toxicol. 2011, 92, 69–76.CrossRefGoogle Scholar
- Huang, K. Y.; Ma, H. L.; Liu, J.; Huo, S. D.; Kumar, A.; Wei, T.; Zhang, X.; Jin, S. B.; Gan, Y. L.; Wang, P. C. et al. Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo. ACS Nano 2012, 6, 4483–4493.CrossRefGoogle Scholar