Open Access Research article

Impaired liver function in Xenopus tropicalis exposed to benzo[a]pyrene: transcriptomic and metabolic evidence

Christophe Regnault123, Isabelle AM Worms4, Christine Oger-Desfeux5, Christelle MelodeLima12, Sylvie Veyrenc123, Marie-Laure Bayle6, Bruno Combourieu6, Aurélie Bonin12, Julien Renaud12, Muriel Raveton123 and Stéphane Reynaud1237*

Author Affiliations

1 University Grenoble Alpes, LECA, F-38000 Grenoble, France

2 CNRS, LECA, F-38000 Grenoble, France

3 University Grenoble Alpes, BEeZy, F-38000 Grenoble, France

4 Université de Genève, Institute F.A. Forel, Versoix, Suisse

5 Pôle Rhône Alpes de Bioinformatique, Université Claude Bernard Lyon 1, Villeurbanne, France

6 Plateforme de recherche en toxicologie environnementale et écotoxicologie de Rovaltain, Valence, France

7 Laboratoire d’Ecologie Alpine (LECA), UMR CNRS-Université de Grenoble 5553, Domaine Universitaire de Saint-Martin d’Hères, 2233, rue de la piscine Bât D Biologie, BP 53, 38041 Grenoble Cedex 9, France

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BMC Genomics 2014, 15:666  doi:10.1186/1471-2164-15-666

Published: 8 August 2014



Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role pollutants play in the decline of amphibian populations remains unclear. Amongst the most common aquatic contaminants, polycyclic aromatic hydrocarbons (PAHs) have been shown to induce several adverse effects on amphibian species in the larval stages. Conversely, adults exposed to high concentrations of the ubiquitous PAH, benzo[a]pyrene (BaP), tolerate the compound thanks to their highly efficient hepatic detoxification mechanisms. Due to this apparent lack of toxic effect on adults, no studies have examined in depth the potential toxicological impact of PAH on the physiology of adult amphibian livers. This study sheds light on the hepatic responses of Xenopus tropicalis when exposed to high environmentally relevant concentrations of BaP, by combining a high throughput transcriptomic approach (mRNA deep sequencing) and a characterization of cellular and physiological modifications to the amphibian liver.


Transcriptomic changes observed in BaP-exposed Xenopus were further characterized using a time-dependent enrichment analysis, which revealed the pollutant-dependent gene regulation of important biochemical pathways, such as cholesterol biosynthesis, insulin signaling, adipocytokines signaling, glycolysis/gluconeogenesis and MAPK signaling. These results were substantiated at the physiological level with the detection of a pronounced metabolic disorder resulting in a possible insulin resistance-like syndrome phenotype. Hepatotoxicity induced by lipid and cholesterol metabolism impairments was clearly identified in BaP-exposed individuals.


Our data suggested that BaP may disrupt overall liver physiology, and carbohydrate and cholesterol metabolism in particular, even after short-term exposure. These results are further discussed in terms of how this deregulation of liver physiology can lead to general metabolic impairment in amphibians chronically exposed to contaminants, thereby illustrating the role xenobiotics might play in the global decline in amphibian populations.

RNA sequencing; Xenopus; Liver; Metabolic disorders; Insulin resistance-like syndrome; Benzo[a]pyrene