Molecular evidence of offspring liver dysfunction after maternal exposure to zinc oxide nanoparticles

Toxicol Appl Pharmacol. 2017 Aug 15:329:318-325. doi: 10.1016/j.taap.2017.06.021. Epub 2017 Jun 23.

Abstract

Recently, reproductive, embryonic and developmental toxicity have been considered as one important sector of nanoparticle (NP) toxicology, with some studies already suggesting varying levels of toxicity and possible transgenerational toxic effects. Even though many studies have investigated the toxic effects of zinc oxide nanoparticles (ZnO NPs), little is known of their impact on overall reproductive outcome and transgenerational effects. Previously we found ZnO NPs caused liver dysfunction in lipid synthesis. This investigation, for the first time, explored the liver dysfunction at the molecular level of gene and protein expression in offspring after maternal exposure to ZnO NPs. Three pathways were investigated: lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis at 5 different time points from embryonic day-18 to postnatal day-20. It was found that the expression of 15, 16, and 16 genes in lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis signalling pathway respectively in F1 animal liver were altered by ZnO NPs compared to ZnSO4. The proteins in these signalling pathways (five in each pathways analyzed) in F1 animal liver were also changed by ZnO NPs compared to ZnSO4. The results suggest that ZnO NPs caused maternal liver defects can also be detected in offspring that might result in problems on offspring liver development, mainly on lipid synthesis, growth, and lesions or apoptosis. Along with others, this study suggests that ZnO NPs may pose reproductive, embryonic and developmental toxicity; therefore, precautions should be taken with regard to human exposure during daily life.

Keywords: Gene expression; Liver dysfunction; Offspring; Protein level; ZnO nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Chemical and Drug Induced Liver Injury / embryology
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chick Embryo
  • Chickens
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lipolysis / drug effects
  • Lipolysis / genetics
  • Liver / drug effects*
  • Liver / embryology
  • Liver / metabolism
  • Maternal Exposure / adverse effects*
  • Metal Nanoparticles / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Assessment
  • Signal Transduction / drug effects
  • Time Factors
  • Zinc Oxide / toxicity*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Zinc Oxide