Research Paper Volume 10, Issue 8 pp 2170—2189

Exposure to Zinc oxide nanoparticles during pregnancy induces oocyte DNA damage and affects ovarian reserve of mouse offspring

Qiu-Yue Zhai 1, *, , Wei Ge 1, *, , Jun-Jie Wang 1, , Xiao-Feng Sun 1, , Jin-Mei Ma 2, , Jing-Cai Liu 1, , Yong Zhao 1, , Yan-Zhong Feng 3, , Paul W. Dyce 4, , Massimo De Felici 5, , Wei Shen 1, ,

  • 1 College of Life Sciences, Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao 266109, China
  • 2 Animal Husbandry and Veterinary Station of Penglai City, Yantai 265600, China
  • 3 Institute of Animal Sciences, Heilongjiang Academy of Agricultural Sciences, Harbin, Heilongjiang 150086, China
  • 4 Department of Animal Sciences, Auburn University, Auburn, AL 36849, USA
  • 5 Department of Biomedicine and Prevention, University of Rome ‘Tor Vergata’, Rome 00133, Italy
* Equal contribution

received: May 15, 2018 ; accepted: June 23, 2018 ; published: August 28, 2018 ;
How to Cite

Copyright: Zhai et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zinc oxide nanoparticles (nZnO) have been shown to have higher toxic effects likely due to their ion-shedding ability and low solubility under neutral conditions. In order to investigate whether exposure to nZnO during embryonic development affects ovary development, 12.5 day post coitum (dpc) fetal mouse ovaries were cultured in the presence of nZnO for 6 days. We found that the nanoparticles (NPs) accumulated within the oocyte cytoplasm in a dose dependent manner, caused DNA damage and apoptosis, and result in a significant decrease in oocyte numbers. No such effects were observed when the ovaries were incubated in the presence of ZnSO4 or bulk ZnO as controls. In addition, we injected intravenously 16 mg/kg body weight nZnO in 12.5 dpc pregnant mice on two consecutive days and analyzed the ovaries of fetuses or offspring at three critical periods of oogenesis: 17.5 dpc, 3 days post-partum (dpp) and 21 dpp. Evidence of increased DNA damage in pachytene oocytes in fetal ovaries and impaired primordial follicle assembly and folliculogenesis dynamics in the ovaries of the offspring were found. Our results indicate that certain types of NPs affect pre- and post-natal oogenesis in vitro and in vivo.


nZnO: zinc oxide nanoparticles; NPs: nanoparticles; dpc: day post coitum; dpp: days post-partum; PGC: primordial germ cell; PCD: programmed cell death; POI: premature ovarian inefficiency; DSBs: DNA double-stand break; TEM: transmission electron microscope; SEM: scanning electron microscope; α-MEM: α-Minimal Essential Medium; FSH: follicle stimulating hormone; GV: Germinal vesicle; PBS: phosphate buffer saline; BSA: bovine serum albumin; IF: immunofluorescence; WB: western blotting.