title: Mono-2-ethylhexyl phthalate disrupts neurulation and modifies the embryonic redox environment and gene expression.
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.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
authors.forename: Karilyn E
authors.initials: KE
authors.lastname: Sant
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Jilek
authors.affiliation: Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Sartor
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States; Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, United States. Electronic address: charris@umich.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Harris
mesh_terms: D000818:Animals; D003545:Cysteine / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D054261:Neurulation / Q000187:drug effects*; D010084:Oxidation-Reduction
chemical_list: D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; D005978:Glutathione; D003545:Cysteine
keywords: Cysteine; DEHP; Embryo; Gene expression; Glutathione; MEHP; Neural tube defects; Redox potential; Visceral yolk sac