Univ. Grenoble-Alpes, Univ. Savoie Mont Blanc, CNRS, LECA, 38000 Grenoble, France.
Univ. Grenoble-Alpes, INSERM, LBFA, 38000 Grenoble, France.
Proc Natl Acad Sci U S A. 2018 May 8;115(19):E4416-E4425. doi: 10.1073/pnas.1721267115. Epub 2018 Apr 23.
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 exposed from tadpole stage to benzo()pyrene or triclosan at concentrations of 50 ng⋅L 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 F animals did indeed have reduced reproductive success, demonstrating a lower fitness in ED-exposed Moreover, after 1 year of depuration, that had been exposed to benzo()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.
尽管有大量研究表明两栖动物对内分泌干扰物 (EDs) 非常敏感,但它们在种群减少中的作用和潜在机制仍不清楚。本研究表明,一生中持续暴露于被认为对饮用水安全的 ED 浓度下的青蛙,会发展出糖尿病前期表型,更常见的是代谢综合征。从蝌蚪期开始就暴露于 50ng/L 的苯并()芘或三氯生的雌性 ,表现出葡萄糖不耐受综合征、肝脂肪变性、肝线粒体功能障碍、肝转录组特征和胰腺胰岛素分泌过多,所有这些都是糖尿病前期的典型特征。这种代谢综合征导致其后代的变态发育延迟,而且个体体型更小、体重更轻,所有这些因素都与成年个体的招募减少和繁殖可能性降低有关。我们发现 F 代动物的繁殖成功率确实降低了,这表明 ED 暴露降低了 的适应性。此外,经过 1 年的净化后,暴露于苯并()芘的 仍然表现出肝损伤和明显的胰岛素分泌缺陷,导致葡萄糖不耐受。我们的研究结果表明,两栖动物对 EDs 的敏感性非常高,即使浓度远低于其他脊椎动物报告的引起应激的阈值。本研究将 EDs 作为导致两栖动物种群减少的一个可能的关键因素,通过代谢紊乱来实现。总的来说,我们的研究结果表明 EDs 会导致代谢紊乱,这与流行病学研究一致,表明环境 EDs 可能是人类代谢性疾病的主要原因之一。