In utero exposure to phenanthrene induces hepatic steatosis in F1 adult female mice

Chemosphere. 2020 Nov;258:127360. doi: 10.1016/j.chemosphere.2020.127360. Epub 2020 Jun 11.


Environmental pollutants are thought to be a risk factor for the prevalence of hepatic steatosis. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, and human exposure is inevitable. In the present study, phenanthrene (Phe) was used as a representative PAH to investigate the effects of in utero exposure to PAH on hepatic lipid metabolism and the toxicological mechanism involved. Pregnant mice (C57BL/6J) were orally administered Phe (0, 60, 600 and 6000 μg kg-1 body weight) once every 3 days with 6 doses in total. F1 female mice aged 125 days showed significantly elevated hepatic lipid levels in the liver. The protein expression of hepatic peroxisome proliferator-activated receptors (PPARβ and PPARγ) and retinoid X receptors (RXRs) was upregulated; the transcription of genes related to lipogenesis, such as srebp1 (encoding sterol regulatory element binding proteins), acca (acetyl-CoA carboxylase), fasn (fatty acid synthase) and pcsk9 (proprotein convertase subtilisin/kexin type 9), showed an upregulation, while the mRNA levels of the lipolysis gene lcat (encoding lecithin cholesterol acyl transferase) were downregulated. These results could be responsible for lipid accumulation. The promoter methylation levels of pparγ were reduced and were the lowest in the 600 μg kg-1 group, and the promoter methylation levels of lcat were significantly increased in all the Phe treatments. These changes were matched with the alterations in their mRNA levels, suggesting that prenatal Phe exposure could induce abnormal lipid metabolism in later life via epigenetic modification.

Keywords: Hepatic steatosis; In utero exposure; Phenanthrene; Polycyclic aromatic hydrocarbon (PAH); Promoter methylation.

MeSH terms

  • Aged, 80 and over
  • Animals
  • Environmental Pollutants / toxicity*
  • Epigenesis, Genetic / drug effects*
  • Fatty Liver / embryology
  • Fatty Liver / metabolism
  • Fatty Liver / virology*
  • Female
  • Humans
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / genetics
  • Lipogenesis / drug effects
  • Lipogenesis / genetics
  • Lipolysis / drug effects
  • Lipolysis / genetics
  • Liver / drug effects
  • Liver / growth & development
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phenanthrenes / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / virology*
  • Transcription, Genetic / genetics


  • Environmental Pollutants
  • Phenanthrenes
  • phenanthrene