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

  • Karilyn E. Sant (a1) (a2), Hadley M. Moreau (a2) (a3), Larissa M. Williams (a3), Haydee M. Jacobs (a2), Anna M. Bowsher (a3), Jason D. Boisvert (a3), Roxanna M. Smolowitz (a4), Jacob Pantazis (a3), Kate Annunziato (a2), Malina Nguyen (a2) and Alicia Timme-Laragy (a2)...

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.

Copyright

Corresponding author

Address for correspondence: Karilyn Sant, School of Public Health, San Diego State University, San Diego, CA92128, USA. Email: ksant@sdsu.edu

References

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

  • Karilyn E. Sant (a1) (a2), Hadley M. Moreau (a2) (a3), Larissa M. Williams (a3), Haydee M. Jacobs (a2), Anna M. Bowsher (a3), Jason D. Boisvert (a3), Roxanna M. Smolowitz (a4), Jacob Pantazis (a3), Kate Annunziato (a2), Malina Nguyen (a2) and Alicia Timme-Laragy (a2)...

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