Mono-2-ethylhexyl phthalate disrupts neurulation and modifies the embryonic redox environment and gene expression

Reprod Toxicol. 2016 Aug:63:32-48. doi: 10.1016/j.reprotox.2016.03.042. Epub 2016 May 7.

Abstract

Mono-2-ethylhexl phthalate (MEHP) is the primary metabolite of di-2-ethylhexyl phthalate (DEHP), a ubiquitous contaminant in plastics. This study sought to determine how structural defects caused by MEHP in mouse whole embryo culture were related to temporal and spatial patterns of redox state and gene expression. MEHP reduced morphology scores along with increased incidence of neural tube defects. Glutathione (GSH) and cysteine (Cys) concentrations fluctuated spatially and temporally in embryo (EMB) and visceral yolk sac (VYS) across the 24h culture. Redox potentials (Eh) for GSSG/GSH were increased by MEHP in EMB (12h) but not in VYS. CySS/CyS Eh in EMB and VYS were significantly increased at 3h and 24h, respectively. Gene expression at 6h showed that MEHP induced selective alterations in EMB and VYS for oxidative phosphorylation and energy metabolism pathways. Overall, MEHP affects neurulation, alters Eh, and spatially alters the expression of metabolic genes in the early organogenesis-stage mouse conceptus.

Keywords: Cysteine; DEHP; Embryo; Gene expression; Glutathione; MEHP; Neural tube defects; Redox potential; Visceral yolk sac.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cysteine / metabolism
  • Diethylhexyl Phthalate / analogs & derivatives*
  • Diethylhexyl Phthalate / toxicity
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Glutathione / metabolism
  • Mice
  • Neurulation / drug effects*
  • Oxidation-Reduction

Substances

  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate
  • Glutathione
  • Cysteine