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

Sant, Karilyn E.; Dolinoy, Dana C.; Jilek, Joseph L.; Sartor, Maureen A.; Harris, Craig

doi:10.1016/j.reprotox.2016.03.042

Cited by 28 publications

(26 citation statements)

References 82 publications

(104 reference statements)

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“…Previous work from our laboratory has demonstrated that exposure to MEHP during early organogenesis may result in stunted growth and delayed or halted neurulation [30]. In this study, nutritional deficiencies were observed as changes in nutrient and cofactor uptake and availability after exposure to MEHP, suggesting that embryonic exposures to toxicants may reduce essential nutrient supplies and produce a canonical stunting of growth.…”

Section: Discussionmentioning

confidence: 56%

“…Mouse embryo culture (mWEC) was performed following the conditions outlined in [31], and described in [30]. Briefly, female CD-1 mice were time-mated and obtained from Charles River (Portage, MI).…”

Section: Methodsmentioning

confidence: 99%

“…This MEHP mixture was diluted in DMSO and added to each treatment culture bottle to produce a final concentration of 100 or 250 µg/ml. These concentrations were optimized from previous experiments [30], based on viability and morphology, as well as reproducibility from other phthalate WEC experiments [29, 32]. Control bottles received an equivalent volume of DMSO only and the total volume added was no greater than 1 µl/ml culture medium.…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations of each analyte were calculated by ratio of the measured analyte to the known quantity of the isotopic standard in each sample. All data was normalized to the total protein concentration of the conceptus to account for the differences in size and morphology due to MEHP treatment [16, 30]. …”

Section: Methodsmentioning

confidence: 99%

“…Numerous studies investigating exposures to DEHP have found detectable levels of its metabolites in a great majority of individuals sampled, including pregnant women [26–28]. Previous studies have demonstrated that MEHP exposure during early organogenesis increased the number of embryos with NTDs [29, 30]. Thus, the purpose of this exploratory work is to identify whether this increased number of NTDs due to MEHP exposure is concordant with decreased nutrient bioavailability to the EMB and whether this may have epigenetic consequences.…”

Section: Introductionmentioning

confidence: 99%

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Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus

Sant

Dolinoy

Jilek

et al. 2016

The Journal of Nutritional Biochemistry

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Histiotrophic nutrition pathways (HNPs) are processes by which the organogenesis-stage conceptus obtains nutrients, amino acids, vitamins, and cofactors required for protein biosynthesis and metabolic activities. Nutrients are captured from the maternal milieu as whole proteins and cargoes via receptor-mediated endocytosis in the visceral yolk sac (VYS), degraded by lysosomal proteolysis, and delivered to the developing embryo (EMB). Several nutrients obtained by HNPs are required substrates for one-carbon (C1) metabolism and supply methyl groups required for epigenetic processes, including DNA and histone methylation. Increased availability of methyl donors has been associated with reduced risk for neural tube defects (NTDs). Here we show that mono-2-ethylhexyl phthalate (MEHP) treatment (100 or 250 µM) alters HNPs, C1 metabolism, and epigenetic programming in the organogenesis-stage conceptus. Specifically, 3 h MEHP treatment of mouse embryos in whole culture resulted in dose dependent reduction of HNP activity in the conceptus. To observe nutrient consequences of decreased HNP function, C1 components and substrates and epigenetic outcomes were quantified at 24 h. Treatment with 100 µM MEHP resulted in decreased dietary methyl donor concentrations, while treatment with 100 or 250 µM MEHP resulted in dose-dependent elevated C1 products and substrates. In MEHP-treated EMBs with NTDs, H3K4 methylation was significantly increased, while no effects were seen in treated VYS. DNA methylation was reduced in MEHP-treated EMB with and without NTDs. This research suggests that environmental toxicants such as MEHP decrease embryonic nutrition in a time-dependent manner, and that epigenetic consequences of HNP disruption may be exacerbated in EMB with NTDs.

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Section: Discussionmentioning

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus

Sant

Dolinoy

Jilek

et al. 2016

The Journal of Nutritional Biochemistry

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Pancreatic beta cells are a sensitive target of embryonic exposure to butylparaben in zebrafish (Danio rerio)

Brown

Sant

Fleischman

et al. 2018

Birth Defects Research

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Migration of Phthalates from Cellulose Packaging into Food Simulant: Assessment of Different Levels of Contaminants

Coltro¹,

Machado

2020

Macromolecular Symposia

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Since paper recycling operates with market‐collected paper scrap, this may lead to undesirable chemicals migrating from the wastepaper into the recycled material. Therefore, this study is based on the assessment of several additives inadvertently included in cellulose packaging that may migrate to foodstuff, considering that toxicological effects of some of these additives may persist in recycled cellulose fibers used to produce new food packaging. The purpose of this study is to determine migration of dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), bis(2‐ethylhexyl) phthalate (DEHP) and 2,6‐diisopropylnaphthalene (DIPN) into fatty food simulant (n‐heptane) by means of gas chromatography with flame ionization detector (GC‐FID). For this purpose, commercial samples of cellulose food packages are contaminated with different concentrations of these additives, and migration into the food simulant is evaluated after the samples remain in contact with the food simulant for a prolonged time at maximum temperatures of 40 °C. The results of the assessment show that an amount ranging from 0.1–0.3% of phthalates and DIPN migrate from the fortified package into the fatty food simulant. The maximum levels of migration of these additives into the recycled cellulose packaging in order to comply with the specific migration limits for contact with foodstuff have been estimated.

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

Cited by 28 publications

References 82 publications

Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus

Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus

Pancreatic beta cells are a sensitive target of embryonic exposure to butylparaben in zebrafish (Danio rerio)

Migration of Phthalates from Cellulose Packaging into Food Simulant: Assessment of Different Levels of Contaminants

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