Metabolome disruption of pregnant rats and their offspring resulting from repeated exposure to a pesticide mixture representative of environmental contamination in Brittany

PLoS One. 2018 Jun 20;13(6):e0198448. doi: 10.1371/journal.pone.0198448. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Carbofuran / adverse effects
  • Chlormequat / adverse effects
  • Disease Models, Animal
  • Environmental Exposure / adverse effects*
  • Female
  • France
  • Glycine / adverse effects
  • Glycine / analogs & derivatives
  • Humans
  • Infectious Disease Transmission, Vertical / statistics & numerical data
  • Lipid Metabolism / drug effects
  • Metabolome / drug effects*
  • Metabolomics / methods*
  • Morpholines / adverse effects
  • Neonicotinoids / adverse effects
  • Nitriles / adverse effects
  • Nitro Compounds / adverse effects
  • Organophosphorus Compounds / adverse effects
  • Oxidative Stress
  • Pesticides / adverse effects*
  • Pregnancy
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Toluidines / adverse effects

Substances

  • Morpholines
  • Neonicotinoids
  • Nitriles
  • Nitro Compounds
  • Organophosphorus Compounds
  • Pesticides
  • Toluidines
  • imidacloprid
  • fenpropimorph
  • glyphosate
  • acetochlor
  • Chlormequat
  • bromoxynil
  • Carbofuran
  • Glycine
  • ethephon

Grant support

This work was supported by grants from the EHESP-School of Public Health (Young Researchers) and the French Ministry of Environment in the national program Grenelle de l’Environnement Programme LOLF 189 Funding (EXPiOmark).