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Proc Natl Acad Sci U S A. 2018 May 8;115(19):E4416-E4425. doi: 10.1073/pnas.1721267115. Epub 2018 Apr 23.

Unexpected metabolic disorders induced by endocrine disruptors in Xenopus tropicalis provide new lead for understanding amphibian decline.

Author information

1
Univ. Grenoble-Alpes, Univ. Savoie Mont Blanc, CNRS, LECA, 38000 Grenoble, France.
2
Univ. Grenoble-Alpes, INSERM, LBFA, 38000 Grenoble, France.
3
Institut de Génomique Fonctionnelle de Lyon, Université Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 69000 Lyon, France.
4
Rovaltain Research Company, F-26300 Alixan, France.
5
Plate-forme Therassay, l'Institut du Thorax, INSERM, CNRS, Université de Nantes, 44007 Nantes, France.
6
Centre de Ressources Biologiques Xénopes, Université Rennes 1, CNRS, Unité Mixte de Service 3387, 35042 Rennes, France.
7
Univ. Grenoble-Alpes, Univ. Savoie Mont Blanc, CNRS, LECA, 38000 Grenoble, France; stephane.reynaud@univ-grenoble-alpes.fr.

Abstract

Despite numerous studies suggesting that amphibians are highly sensitive to endocrine disruptors (EDs), both their role in the decline of populations and the underlying mechanisms remain unclear. This study showed that frogs exposed throughout their life cycle to ED concentrations low enough to be considered safe for drinking water, developed a prediabetes phenotype and, more commonly, a metabolic syndrome. Female Xenopus tropicalis exposed from tadpole stage to benzo(a)pyrene or triclosan at concentrations of 50 ng⋅L-1 displayed glucose intolerance syndrome, liver steatosis, liver mitochondrial dysfunction, liver transcriptomic signature, and pancreatic insulin hypersecretion, all typical of a prediabetes state. This metabolic syndrome led to progeny whose metamorphosis was delayed and occurred while the individuals were both smaller and lighter, all factors that have been linked to reduced adult recruitment and likelihood of reproduction. We found that F1 animals did indeed have reduced reproductive success, demonstrating a lower fitness in ED-exposed Xenopus Moreover, after 1 year of depuration, Xenopus that had been exposed to benzo(a)pyrene still displayed hepatic disorders and a marked insulin secretory defect resulting in glucose intolerance. Our results demonstrate that amphibians are highly sensitive to EDs at concentrations well below the thresholds reported to induce stress in other vertebrates. This study introduces EDs as a possible key contributing factor to amphibian population decline through metabolism disruption. Overall, our results show that EDs cause metabolic disorders, which is in agreement with epidemiological studies suggesting that environmental EDs might be one of the principal causes of metabolic disease in humans.

KEYWORDS:

Xenopus tropicalis; amphibian population decline; endocrine disruptors; metabolic syndrome; transgenerational

PMID:
29686083
PMCID:
PMC5948982
DOI:
10.1073/pnas.1721267115
[Indexed for MEDLINE]
Free PMC Article

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