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

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 24 h culture. Redox potentials (E-h) for GSSG/GSH were increased by MEHP in EMB (12 h) but not in VYS. CySS/CyS E-h in EMB and VYS were significantly increased at 3 h and 24 h, respectively. Gene expression at 6 h showed that MEHP induced selective alterations in EMB and VYS for oxidative phosphorylation and energy metabolism pathways. Overall, MEHP affects neurulation, alters E-h, and spatially alters the expression of metabolic genes in the early organogenesis-stage mouse conceptus. (C) 2016 Elsevier Inc. All rights reserved.