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

Francesca Maranghi, Stefano Lorenzetti, Roberta Tassinari, Gabriele Moracci, Valentina Tassinari, Daniele Marcoccia, Antonio Di Virgilio, Agostino Eusepi, Antonella Romeo, Armando Magrelli, Marco Salvatore, Fabrizio Tosto, Mara Viganotti, Antonio Antoccia, Alessandra Di Masi, Gianluca Azzalin, Caterina Tanzarella, Giuseppe Macino, Domenica Taruscio, Alberto Mantovani

Research output: Contribution to journalArticle

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 α-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 β-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 β-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.

Original languageEnglish
Pages (from-to)427-432
Number of pages6
JournalReproductive Toxicology
Volume29
Issue number4
DOIs
Publication statusPublished - Jul 2010

Keywords

  • α-Fetoprotein
  • β-Catenin
  • Benzofuran
  • DEHP
  • Glycogen storage
  • Hepatosteatosis
  • Liver programming

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

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    Maranghi, F., Lorenzetti, S., Tassinari, R., Moracci, G., Tassinari, V., Marcoccia, D., Di Virgilio, A., Eusepi, A., Romeo, A., Magrelli, A., Salvatore, M., Tosto, F., Viganotti, M., Antoccia, A., Di Masi, A., Azzalin, G., Tanzarella, C., Macino, G., Taruscio, D., & Mantovani, A. (2010). In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. Reproductive Toxicology, 29(4), 427-432. https://doi.org/10.1016/j.reprotox.2010.03.002