In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice

Reprod Toxicol. 2010 Jul;29(4):427-32. doi: 10.1016/j.reprotox.2010.03.002. Epub 2010 Mar 20.

Abstract

The plasticizer di-(2-ethylhexyl)phthalate (DEHP) affects reproductive development, glycogen and lipid metabolism. Whereas liver is a main DEHP target in adult rodents, the potential impact on metabolic programming is unknown. Effects of in utero DEHP exposure on liver development were investigated upon treatment of pregnant CD-1 mice on gestational days (GD)11-19. F1 mice were examined at post-natal days 21 (weaning) and 35 (start of puberty): parameters included liver histopathological, immunocytochemical and alpha-fetoprotein (AFP) gene expression analyses. In utero DEHP exposure altered post-natal liver development in weanling mice causing significant, dose-related (i) increased hepatosteatosis, (ii) decreased glycogen storage, (iii) increased beta-catenin intracytoplasmic localization (females only). At puberty, significantly decreased glycogen storage was still present in males. A treatment-induced phenotype was identified with lack of glycogen accumulation and intracytoplasmic localization of beta-catenin which was associated with increased AFP gene expression. Our findings suggested that DEHP alters post-natal liver development delaying the programming of glycogen metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytoplasm / metabolism
  • Diethylhexyl Phthalate / toxicity*
  • Environmental Pollutants / toxicity*
  • Fatty Liver / chemically induced*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Gene Expression / drug effects
  • Liver / drug effects*
  • Liver / growth & development
  • Liver / metabolism
  • Liver Glycogen / metabolism
  • Maternal Exposure
  • Mice
  • Mice, Inbred Strains
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / metabolism
  • RNA, Messenger / metabolism
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / metabolism
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, mouse
  • Environmental Pollutants
  • Liver Glycogen
  • RNA, Messenger
  • alpha-Fetoproteins
  • beta Catenin
  • Diethylhexyl Phthalate