title: Metabolomics tools for describing complex pesticide exposure in pregnant women in Brittany (France).
abstract: BACKGROUND
  The use of pesticides and the related environmental contaminations can lead to human exposure to various molecules. In early-life, such exposures could be responsible for adverse developmental effects. However, human health risks associated with exposure to complex mixtures are currently under-explored.
  
  
  OBJECTIVE
  THIS PROJECT AIMS AT ANSWERING THE FOLLOWING QUESTIONS: What is the influence of exposures to multiple pesticides on the metabolome? What mechanistic pathways could be involved in the metabolic changes observed?
  
  
  METHODS
  Based on the PELAGIE cohort (Brittany, France), 83 pregnant women who provided a urine sample in early pregnancy, were classified in 3 groups according to the surface of land dedicated to agricultural cereal activities in their town of residence. Nuclear magnetic resonance-based metabolomics analyses were performed on urine samples. Partial Least Squares Regression-Discriminant Analysis (PLS-DA) and polytomous regressions were used to separate the urinary metabolic profiles from the 3 exposure groups after adjusting for potential confounders.
  
  
  RESULTS
  The 3 groups of exposure were correctly separated with a PLS-DA model after implementing an orthogonal signal correction with pareto standardizations (R2 = 90.7% and Q2 = 0.53). After adjusting for maternal age, parity, body mass index and smoking habits, the most statistically significant changes were observed for glycine, threonine, lactate and glycerophosphocholine (upward trend), and for citrate (downward trend).
  
  
  CONCLUSIONS
  This work suggests that an exposure to complex pesticide mixtures induces modifications of metabolic fingerprints. It can be hypothesized from identified discriminating metabolites that the pesticide mixtures could increase oxidative stress and disturb energy metabolism.
authors.affiliation: National Institute of Health and Medical Research (INSERM) UMR 1085 IRSET (Research Institute for Environmental and Occupational Health), Rennes, France. nathalie.bonvallot@ehesp.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonvallot
authors.forename: Marie
authors.initials: M
authors.lastname: Tremblay-Franco
authors.forename: Cécile
authors.initials: C
authors.lastname: Chevrier
authors.forename: Cécile
authors.initials: C
authors.lastname: Canlet
authors.forename: Charline
authors.initials: C
authors.lastname: Warembourg
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cravedi
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Cordier
mesh_terms: D000328:Adult; D016002:Discriminant Analysis; D005260:Female; D005602:France; D006801:Humans; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D018811:Maternal Exposure / Q000009:adverse effects*; D055432:Metabolomics / Q000379:methods*; D010575:Pesticides / Q000652:urine*; D011247:Pregnancy; D037841:Pregnant People
chemical_list: D010575:Pesticides