title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea ; College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People's Republic of China.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Sangiliyandi
authors.initials: S
authors.lastname: Gurunathan
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D001483:Base Sequence; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018392:Genomic Imprinting / Q000187:drug effects; D006801:Humans; D049469:Meiotic Prophase I / Q000187:drug effects; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000648:ultrastructure; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010053:Ovary / Q000166:cytology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012834:Silver / Q000009:adverse effects*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D012834:Silver
keywords: gene expression; meiosis; methylation; silver nanoparticles