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Proc Natl Acad Sci U S A 2018 May 08;11519:E4416-E4425. doi: 10.1073/pnas.1721267115.
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Unexpected metabolic disorders induced by endocrine disruptors in Xenopus tropicalis provide new lead for understanding amphibian decline.

Regnault C , Usal M , Veyrenc S , Couturier K , Batandier C , Bulteau AL , Lejon D , Sapin A , Combourieu B , Chetiveaux M , Le May C , Lafond T , Raveton M , Reynaud S .

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.

PubMed ID: 29686083
PMC ID: PMC5948982
Article link: Proc Natl Acad Sci U S A

Species referenced: Xenopus tropicalis
Genes referenced: acss2.2 calr cd3e cd40 dhcr7 dnajb11 dnajb9 dnajc3 dnajc9 elovl2 fas g6pc1.2 gadd45g grhpr.1 hmgcs1 hsp90b1 hspa5 igfbp1 ins mgat2 nr4a1 nr4a2 pdia4 pnpla3 sult2b1 susd1 vasp vegfc
GO keywords: glucose metabolic process [+]

Disease Ontology terms: nonalcoholic fatty liver disease

Article Images: [+] show captions
References [+] :
Alonso-Magdalena, Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. 2010, Pubmed