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

Published online by Cambridge University Press:  17 February 2020

Karilyn E. Sant Open the ORCID record for Karilyn E. Sant [Opens in a new window] ,
Hadley M. Moreau ,
Larissa M. Williams ,
Haydee M. Jacobs ,
Anna M. Bowsher ,
Jason D. Boisvert ,
Roxanna M. Smolowitz ,
Jacob Pantazis ,
Kate Annunziato  and
Malina Nguyen
...Show all authors
Karilyn E. Sant*
Affiliation:
Division of Environmental Health, School of Public Health, San Diego State University, San Diego92182, CA, USA Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA
Hadley M. Moreau
Affiliation:
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA Department of Biology, Bates College, Lewiston04240, ME, USA
Larissa M. Williams
Affiliation:
Department of Biology, Bates College, Lewiston04240, ME, USA
Haydee M. Jacobs
Affiliation:
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA
Anna M. Bowsher
Affiliation:
Department of Biology, Bates College, Lewiston04240, ME, USA
Jason D. Boisvert
Affiliation:
Department of Biology, Bates College, Lewiston04240, ME, USA
Roxanna M. Smolowitz
Affiliation:
Department of Biology, Roger Williams University, Bristol02809, RI, USA
Jacob Pantazis
Affiliation:
Department of Biology, Bates College, Lewiston04240, ME, USA
Kate Annunziato
Affiliation:
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA
Malina Nguyen
Affiliation:
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA
Alicia Timme-Laragy
Affiliation:
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst01003, MA, USA
*
Address for correspondence: Karilyn Sant, School of Public Health, San Diego State University, San Diego, CA92128, USA. Email: [email protected]
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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.

Keywords

PhthalateMEHPNrf2embryozebrafishlipid accumulationsteatosisDOHaD
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 1 , February 2021 , pp. 132 - 140
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Copyright
© The Author(s) 2020. Published by Cambridge University Press and the International Society for Developmental Origins of Health and Disease

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