PUBLICATION

Embryonic exposures to mono-2-ethylhexyl phthalate induce larval steatosis in zebrafish independent of Nrf2a signaling

Authors
Sant, K.E., Moreau, H.M., Williams, L.M., Jacobs, H.M., Bowsher, A.M., Boisvert, J.D., Smolowitz, R.M., Pantazis, J., Annunziato, K., Nguyen, M., Timme-Laragy, A.
ID
ZDB-PUB-200221-14
Date
2020
Source
Journal of developmental origins of health and disease   12(1): 132-140 (Journal)
Registered Authors
Keywords
DOHaD, MEHP, Nrf2, Phthalate, embryo, lipid accumulation, steatosis, zebrafish
MeSH Terms
  • NF-E2-Related Factor 2/genetics
  • NF-E2-Related Factor 2/metabolism*
  • Lipid Metabolism/drug effects
  • Animals, Genetically Modified
  • Disease Models, Animal
  • Maternal Exposure/adverse effects*
  • Female
  • Fatty Liver/chemically induced*
  • Fatty Liver/pathology
  • Diethylhexyl Phthalate/analogs & derivatives*
  • Diethylhexyl Phthalate/toxicity
  • Signal Transduction/drug effects
  • Larva/drug effects
  • Larva/metabolism
  • Oxidative Stress/drug effects
  • Animals
  • Gene Expression Regulation, Developmental/drug effects
  • Humans
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Loss of Function Mutation
  • Fatty Acid-Binding Proteins/metabolism
(all 22)
PubMed
32063256 Full text @ J Dev Orig Health Dis
Abstract
Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.
Genes / Markers
Figures
No images available
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh318
    		Point Mutation
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Fish
    Antibodies
    Orthology
    Engineered Foreign Genes
    No data available
    Mapping
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    Citation
    Sant, K.E., Moreau, H.M., Williams, L.M., Jacobs, H.M., Bowsher, A.M., Boisvert, J.D., Smolowitz, R.M., Pantazis, J., Annunziato, K., Nguyen, M., Timme-Laragy, A. (2020) Embryonic exposures to mono-2-ethylhexyl phthalate induce larval steatosis in zebrafish independent of Nrf2a signaling. Journal of developmental origins of health and disease. 12(1):132-140.