Department or Program

Environmental Studies

Abstract

Phthalates are plasticizers and ubiquitous human toxicants. Mono(2-ethylhexyl) phthalate (MEHP) has been linked to abnormal development, increased oxidative stress, and metabolic syndrome. Nuclear Factor, Erythroid 2 Like 2 (Nrf2) is a transcription factor that regulates gene expression in response to oxidative stress and is duplicated in zebrafish. The objective of this study was to investigate the role of one Nrf2 paralog, Nrf2a, in juvenile adiposity following embryonic exposure to MEHP. Zebrafish (Danio rerio) wild type (wt) and mutant (m) embryos from a Nrf2a mutant line were exposed to 0 or 200 μg/L MEHP through immersion beginning at 6 hours post fertilization (hpf) and concluding at 120 hpf. At 120 hpf fish were placed in clean system water and maintained to 15 days post fertilization (dpf). At 15 dpf fish were imaged for length and stained with Oil Red O to visualize neural lipid depots, and gene expression analysis was conducted via qPCR. MEHP exposure and mutated Nrf2a attenuated fish length, and MEHP exposure significantly increased hepatic steatosis in both exposed wild-type and Nrf2a mutant fish, an effect that was exacerbated in mutants. Reduced expression of both pparα and pparγ in the MEHP exposed group may indicate crosstalk between Nrf2a and PPARs.

These data indicate developmental exposure to MEHP may increase risk for hepatic steatosis, and that impaired Nrf2a function may exacerbate this phenotype. Our data suggest that toxicant-induced oxidative stress during embryonic development is a risk factor for hepatic steatosis later in life, and Nrf2 function is important for mitigating this stress and decreasing risk for hepatic steatosis.

Level of Access

Restricted: Archival Copy [No Access]

First Advisor

Larissa Williams

Date of Graduation

5-2019

Degree Name

Bachelor of Arts

Number of Pages

48

Embargoed

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