PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

Toxicology. 2011 Mar 28;282(1-2):23-9. doi: 10.1016/j.tox.2011.01.011. Epub 2011 Jan 18.


Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain heart function. The results indicate PFOS prenatal exposure can induce cardiac mitochondrial injury and gene transcript change, which may be a significant mechanism of the developmental toxicity of PFOS to rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonic Acids / administration & dosage
  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Cardiotoxins / administration & dosage
  • Cardiotoxins / toxicity*
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / administration & dosage
  • Environmental Pollutants / toxicity
  • Female
  • Fluorocarbons / administration & dosage
  • Fluorocarbons / toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Heart / drug effects*
  • Heart / growth & development
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / ultrastructure
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Surface-Active Agents / administration & dosage
  • Surface-Active Agents / toxicity
  • Vacuoles / drug effects
  • Weaning


  • Alkanesulfonic Acids
  • Cardiotoxins
  • Environmental Pollutants
  • Fluorocarbons
  • Mitochondrial Proteins
  • RNA, Messenger
  • Surface-Active Agents
  • perfluorooctane sulfonic acid