PMID- 29924815 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20231213 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 6 DP - 2018 TI - Metabolome disruption of pregnant rats and their offspring resulting from repeated exposure to a pesticide mixture representative of environmental contamination in Brittany. PG - e0198448 LID - 10.1371/journal.pone.0198448 [doi] LID - e0198448 AB - 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 mug/kg bw/d) + bromoxynil (12 mug/kg bw/d) + carbofuran (22.5 mug/kg bw/d) + chlormequat (35 mug/kg bw/d) + ethephon (22.5 mug/kg bw/d) + fenpropimorph (15.5 mug/kg bw/d) + glyphosate (12 mug/kg bw/d) + imidacloprid (12.5 mug/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. FAU - Bonvallot, Nathalie AU - Bonvallot N AUID- ORCID: 0000-0002-8070-6008 AD - Univ Rennes, EHESP, Inserm, Irset (Institut de recherche en sante, environnement et travail)-UMR_S 1085, Rennes, France. AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Canlet, Cecile AU - Canlet C AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Blas-Y-Estrada, Florence AU - Blas-Y-Estrada F AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Gautier, Roselyne AU - Gautier R AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Tremblay-Franco, Marie AU - Tremblay-Franco M AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Chevolleau, Sylvie AU - Chevolleau S AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. FAU - Cordier, Sylvaine AU - Cordier S AD - Univ Rennes, EHESP, Inserm, Irset (Institut de recherche en sante, environnement et travail)-UMR_S 1085, Rennes, France. FAU - Cravedi, Jean-Pierre AU - Cravedi JP AD - INRA UMR 1331 Toxalim, University of Toulouse, INP, ENVT, EIP, UPS, UMR1331, Toulouse, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180620 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Morpholines) RN - 0 (Neonicotinoids) RN - 0 (Nitriles) RN - 0 (Nitro Compounds) RN - 0 (Organophosphorus Compounds) RN - 0 (Pesticides) RN - 0 (Toluidines) RN - 3BN7M937V8 (imidacloprid) RN - 4548UM725F (fenpropimorph) RN - 8L08WMO94K (acetochlor) RN - 8SUZ1123XX (Chlormequat) RN - J46EK95K0P (bromoxynil) RN - SKF77S6Y67 (Carbofuran) RN - TE7660XO1C (Glycine) RN - XU5R5VQ87S (ethephon) SB - IM MH - Animals MH - Animals, Newborn MH - Carbofuran/adverse effects MH - Chlormequat/adverse effects MH - Disease Models, Animal MH - Environmental Exposure/*adverse effects MH - Female MH - France MH - Glycine/adverse effects/analogs & derivatives MH - Humans MH - Infectious Disease Transmission, Vertical/statistics & numerical data MH - Lipid Metabolism/drug effects MH - Metabolome/*drug effects MH - Metabolomics/*methods MH - Morpholines/adverse effects MH - Neonicotinoids/adverse effects MH - Nitriles/adverse effects MH - Nitro Compounds/adverse effects MH - Organophosphorus Compounds/adverse effects MH - Oxidative Stress MH - Pesticides/*adverse effects MH - Pregnancy MH - Proton Magnetic Resonance Spectroscopy MH - Rats MH - Toluidines/adverse effects MH - Glyphosate PMC - PMC6010212 COIS- The authors have declared that no competing interests exist. EDAT- 2018/06/21 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/06/20 CRDT- 2018/06/21 06:00 PHST- 2017/09/18 00:00 [received] PHST- 2018/05/18 00:00 [accepted] PHST- 2018/06/21 06:00 [entrez] PHST- 2018/06/21 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/20 00:00 [pmc-release] AID - PONE-D-17-32481 [pii] AID - 10.1371/journal.pone.0198448 [doi] PST - epublish SO - PLoS One. 2018 Jun 20;13(6):e0198448. doi: 10.1371/journal.pone.0198448. eCollection 2018.