Silver nanoparticles cause complications in pregnant mice

Abstract

Background

Silver nanoparticles (AgNPs) have attracted much interest and have been used for antibacterial, antifungal, anticancer, and antiangiogenic applications because of their unique properties. The increased usage of AgNPs leads to a potential hazard to human health. However, the potential effects of AgNPs on animal models are not clear. This study was designed to investigate the potential impact of AgNPs on pregnant mice.

Methods

The synthesis of AgNPs was performed using culture extracts of Bacillus cereus. The synthesized AgNPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. AgNPs were administrated into pregnant mice via intravenous infusion at 1.0 mg/kg doses at 6.5 days postcoitum (dpc). At 13.5, 15.5, and 17.5 dpc, the pregnant mice were euthanized, and the embryo and placenta were isolated. The meiotic status of oocytes was evaluated. DNA methylation studies were performed, and aberrant imprinting disrupted fetal, placental, and postnatal development. Quantitative real-time polymerase chain reaction analysis and Western blot were used to analyze various gene expressions.

Results

The synthesized AgNPs were uniformly distributed and were spherical in shape with an average size of 8 nm. AgNPs exposure increased the meiotic progression of female germ cells in the fetal mouse ovaries, and maternal AgNP exposure significantly disrupted imprinted gene expression in 15.5 dpc embryos and placentas, such as Ascl2, Snrpn, Kcnq1ot1, Peg3, Zac1, H19, Igf2r, and Igf2; DNA methylation studies revealed that AgNPs exposure significantly altered the methylation levels of differentially methylated regions of Zac1.

Conclusion

The results from this study indicated that early exposure to AgNPs has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta. These results can contribute to research involved in the safe use of various biomedical applications of AgNPs and improves the understanding of the development of AgNPs in biomedical applications.

Keywords:

• silver nanoparticles
• methylation
• meiosis
• gene expression

Supplementary material

Figure S1 Samples from the control and AgNP-treated group placentas on the male mouse at 15.5 dpc were analyzed for total expression of the imprinted genes.

Notes: The relative mRNA expression of the imprinted genes (Ascl2, Snrpn, Kcnq1ot1, Peg3, Zac1, H19, Igf2r, and Igf2) in placentas (n=8 in control group; n=7 in AgNPs-treated group). The results are presented as means ± SD. *P<0.05; **P<0.01.

Abbreviations: AgNPs, silver nanoparticles; SD, standard deviation; dpc, days postcoitum; mRNA, messenger RNA.

Acknowledgments

This paper was supported by the KU – Research Professor Program of the Konkuk University. Dr Sangiliyandi Gurunathan received support from a Konkuk University KU – Full-time Professorship. This work was also supported by the Science Research Center (2015R1A5A1009701) from the National Research Foundation of Korea and the Woo Jang-Choon project (PJ007849) from the Rural Development Administration, Republic of Korea.

Disclosure

The authors report no conflicts of interest in this work.