Univ Rennes, EHESP, Inserm, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Rennes, France.
INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France.
PLoS One. 2018 Jun 20;13(6):e0198448. doi: 10.1371/journal.pone.0198448. eCollection 2018.
The use of pesticides exposes humans to numerous harmful molecules. Exposure in early-life may be responsible for adverse effects in later life. This study aimed to assess the metabolic modifications induced in pregnant rats and their offspring by a pesticide mixture representative of human exposure. Ten pregnant rats were exposed to a mixture of eight pesticides: acetochlor (246 μg/kg bw/d) + bromoxynil (12 μg/kg bw/d) + carbofuran (22.5 μg/kg bw/d) + chlormequat (35 μg/kg bw/d) + ethephon (22.5 μg/kg bw/d) + fenpropimorph (15.5 μg/kg bw/d) + glyphosate (12 μg/kg bw/d) + imidacloprid (12.5 μg/kg bw/d) representing the main environmental pesticide exposure in Brittany (France) in 2004. Another group of 10 pregnant rats served as controls. Females were fed ad libitum from early pregnancy, which is from gestational day (GD) 4 to GD 21. Urine samples were collected at GD 15. At the end of the exposure, mothers and pups were euthanized and blood, liver, and brain samples collected. 1H NMR-based metabolomics and GC-FID analyses were performed and PCA and PLS-DA used to discriminate between control and exposed groups. Metabolites for which the levels were significantly modified were then identified using the Kruskal-Wallis test, and p-values were adjusted for multiple testing correction using the False Discovery Rate. The metabolomics analysis revealed many differences between dams of the two groups, especially in the plasma, liver and brain. The modified metabolites are involved in TCA cycle, energy production and storage, lipid and carbohydrate metabolism, and amino-acid metabolism. These modifications suggest that the pesticide mixture may induce oxidative stress associated with mitochondrial dysfunction and the impairment of glucose and lipid metabolism. These observations may reflect liver dysfunction with increased relative liver weight and total lipid content. Similar findings were observed for glucose and energy metabolism in the liver of the offspring, and oxidative stress was also suggested in the brains of male offspring.
农药的使用使人类接触到许多有害分子。生命早期的接触可能是导致生命后期出现不良影响的原因。本研究旨在评估一种代表人类暴露的农药混合物对怀孕大鼠及其后代的代谢改变。十只怀孕大鼠接触了八种农药的混合物：乙草胺（246μg/kg bw/d）+溴苯腈（12μg/kg bw/d）+克百威（22.5μg/kg bw/d）+矮壮素（35μg/kg bw/d）+乙烯利（22.5μg/kg bw/d）+ 苯醚甲环唑（15.5μg/kg bw/d）+草甘膦（12μg/kg bw/d）+ 氯噻啉（12.5μg/kg bw/d），这代表了 2004 年法国布列塔尼地区主要的环境农药暴露。另一组 10 只怀孕大鼠作为对照组。雌性大鼠从妊娠早期（GD4 至 GD21）自由进食。在 GD15 收集尿液样本。暴露结束时，处死母鼠和幼鼠，采集血液、肝脏和大脑样本。采用基于 1H NMR 的代谢组学和 GC-FID 分析，并使用 PCA 和 PLS-DA 来区分对照组和暴露组。然后使用 Kruskal-Wallis 检验鉴定水平显著改变的代谢物，并使用 False Discovery Rate 对多重检验校正进行 p 值调整。代谢组学分析显示两组母鼠之间存在许多差异，尤其是在血浆、肝脏和大脑中。修饰的代谢物参与 TCA 循环、能量产生和储存、脂质和碳水化合物代谢以及氨基酸代谢。这些修饰表明，农药混合物可能会引起与线粒体功能障碍和葡萄糖及脂质代谢受损相关的氧化应激。这些观察结果可能反映了肝脏功能障碍，表现为相对肝重和总脂质含量增加。在后代的肝脏中也观察到葡萄糖和能量代谢的类似变化，并提示雄性后代的大脑存在氧化应激。
