Embryonic exposures to mono-2-ethylhexyl phthalate induce larval steatosis in zebrafish independent of Nrf2a signaling
Document Type
Article
Publication Title
Journal of Developmental Origins of Health and Disease
Publication Date
2-1-2021
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.
Volume
12
Issue
1
Last Page
140
DOI
10.1017/S2040174420000057
Recommended Citation
Sant, K., Moreau, H., Williams, L., Jacobs, H., Bowsher, A., Boisvert, J., Smolowitz, R., Pantazis, J., Annunziato, K., Nguyen, M., & Timme-Laragy, A. (2021). 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) https://doi.org/10.1017/S2040174420000057
ISSN
20401744
E-ISSN
20401752
Funding Sponsor
National Institutes of Health
Funding Number
P20 GM103423