Exposure to retene, fluoranthene, and their binary mixture causes distinct transcriptomic and apical outcomes in rainbow trout (Oncorhynchus mykiss) yolk sac alevins.

Andreas N.M Eriksson,Aleksei Krasnov,Cyril Rigaud,Emma Wincent,Eeva-Riikka Vehniäinen

doi:10.1016/j.aquatox.2022.106083

Andreas N.M Eriksson, Aleksei Krasnov + Show 3 more

Open Access

https://doi.org/10.1016/j.aquatox.2022.106083

Copy DOI

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are widely spread environmental contaminants which affect developing organisms. It is known that improper activation of the aryl hydrocarbon receptor (AhR) by some PAHs contributes to toxicity, while other PAHs can disrupt cellular membrane function. The exact downstream mechanisms of AhR activation remain unresolved, especially with regard to cardiotoxicity. By exposing newly hatched rainbow trout alevins (Oncorhynchus mykiss) semi-statically to retene (32µg l-1; AhR agonist), fluoranthene (50µg l-1; weak AhR agonist and CYP1a inhibitor) and their binary mixture for 1, 3, 7 and 14 days, we aimed to uncover novel mechanisms of cardiotoxicity using a targeted microarray approach. At the end of the exposure, standard length, yolk area, blue sac disease (BSD) index and PAH body burden were measured, while the hearts were prepared for microarray analysis. Each exposure produced a unique toxicity profile. We observed that retene and the mixture, but not fluoranthene, significantly reduced growth by Day 14 compared to the control, while exposure to the mixture increased the BSD-index significantly from Day 3 onward. Body burden profiles were PAH-specific and correlated well with the exposure-specific upregulations of genes encoding for phase I and II enzymes. Exposure to the mixture over-represented pathways related to growth, amino acid and xenobiotic metabolism and oxidative stress responses. Alevins exposed to the individual PAHs displayed over-represented pathways involved in receptor signaling: retene downregulated genes with a role in G-protein signaling, while fluoranthene upregulated those involved in GABA signaling. Furthermore, exposure to retene and fluoranthene altered the expression of genes encoding for proteins involved in calcium- and potassium ion channels, which suggests affected heart structure and function. This study provides deeper understanding of the complexity of PAH toxicity and the necessity of investigating PAHs as mixtures and not as individual components.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are a widespread group of environmental contaminants of either natural or anthropogenic origin
As expected per previous research (Billiard et al, 2008; Van Tiem and Di Giulio, 2011), the binary mixture produced a stronger toxicity response and a modulated body burden profile compared to exposure to the individual components
Exposure to the PAHs alone, but not the mixture, produced several differently expressed genes (DEGs) that are known to be involved in maintaining heart function and development

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are a widespread group of environmental contaminants of either natural or anthropogenic origin. The environmental prevalence of PAHs has increased over the last century due to increased anthropogenic activities (Wickstrom and Tolonen, 1987; Van Metre et al, 2000). Exposure to PAHs during early life development of fish is well known to result in a broad suite of defects at multiple levels of biological or ganization and increased mortality. Heart structure and function are especially sensitive to PAHs (Incardona et al, 2011), which has multiple down-stream consequences for the growing fish larvae as circulation of nutrients and gas-exchange become restricted. Other developmental defects associated with PAH exposure are genotoxicity and behavioral alter ations (Rhodes et al, 2005; Geier et al, 2018)

Objectives

Methods

Results

Conclusion