Flowchart of the metabolomics analysis.

<p>Flowchart of the metabolomics analysis.</p

Graphical summary of the correlation between X and Y for the first two components.

<p>The correlation between X and Y (w*c) is represented by the loading plot. The PLS-DA model used was constructed on OSC-filtered and Pareto scaled data (N = 83; R2 = 90.7% and Q2 = 0.53), from the ¹H NMR urinary metabolic profiles from 83 pregnant women differently exposed to pesticides.</p

PLS-DA score plot from the ¹H NMR urinary metabolic profiles from 83 pregnant women.

<p>The score plot is the projection of the observations onto the first two latent variables. The PLS-DA model, constructed on OSC-filtered and Pareto-scaled data, includes 4 latent variables (N = 83; R2 = 90.7% and Q2 = 0.53). Three groups according to the percentage of the surface of land dedicated to cereal crops in the town of residence in early pregnancy: purple: group 0: 0–17%, green: group 1: >17–25%; orange: group 2: >25%.</p

Suggested mechanisms of action of complex and low-dose pesticide mixtures.

<p>These suggestions are based on the modification of ¹H NMR urinary metabolic profile of pregnant women.</p

Characteristics of the 83 pregnant women included in the metabolomic study by group of exposure^a.

a<p>Three groups according to the percentage of the surface of land dedicated to cereal crops in the town of residence in early pregnancy: group 0: 0–17%, group 1: >17–25% and group 2: >25%.</p>b<p>p-value of a Fisher exact test.</p>c<p>p-value of a Kruskal-Wallis test.</p

Urinary metabolites discriminated between the 3 groups of pesticide exposures (assessed from the percentage of the surface of land dedicated to cereal crops in the town of residence in early pregnancy) with a PLS-DA model including 4 latent variables on Pareto scaled data (N = 83; R2 = 90.7% and Q2 = 0.53), after an orthogonal signal correction.

<p>Abbreviation: GPC: glycerophosphocholine. The trends are observed after an OSC filtering. The significance was assessed with a non-parametric Kruskal-Wallis test (threshold 0.05).</p

Association between urinary metabolite changes in pregnant women and exposure to pesticides (assessed from the percentage of the surface of land dedicated to cereal crops in the town of residence in early pregnancy).

a<p>Adjusted for maternal age, body mass index, parity and smoking status.</p

Additional file 1: of Occupational exposure to organic solvents during pregnancy and childhood behavior: findings from the PELAGIE birth cohort (France, 2002–2013)

Figure S1. Flow chart of sample selection (PELAGIE Cohort, France, 2002–2013). Table S1. Items used to assess the child behavior at age 2 in the PELAGIE cohort study, France, 2002–2013. Table S2. Items used to assess the mother-child interaction at age 2 in the PELAGIE cohort study, France, 2002–2013. Table S3. Groups of products related to occupational exposure to solvents (n = 715) in the PELAGIE Cohort study, France, 2002–2013. Table S4. Distribution of maternal occupations during pregnancy in the PELAGIE Cohort, France, 2002–2013. Table S5. Characteristics of samples across the PELAGIE Cohort follow-ups (France, 2002–2013). Table S6. Associations between behavior latent traits at 2 and 6 years (crude and adjusted models), PELAGIE Cohort, France, 2002–2013, N = 715. Table S7. Structural Equation Modeling of behavior at ages 2 and 6 in the PELAGIE Cohort, France, 2002–2013 – Factor loadings for the latent traits at ages 2 and 6 (crude and adjusted model, n = 715). Table S8. Structural Equation Modeling of behavior at ages 2 and 6 in the PELAGIE Cohort. France. 2002–2013 – Factor loadings for the latent traits at ages 2 and 6 (crude model) in boys (N = 379) and girls (N = 336). Table S9. Associations between behavior latent traits at age 6 and age 2 in boys (N = 379) and girls (N = 336) (crude model), PELAGIE Cohort, France, 2002–2013. Table S10. Sex-Stratified Total Associations Between Occupational Solvent Exposure During Pregnancy and Child Behavior at Age 2 and Age 6 (N = 379 Boys and N = 336 Girls, PELAGIE cohort, France, 2002–2013). Table S11. Comparison of children participating at the 2 year and 6 year follow-ups with those participating only at the 2 year follow-up (PELAGIE Cohort, France, 2002–2013). (DOCX 131 kb

Two-dimensional PLS-DA and PCA scores plot of pregnant rat samples integrated ¹H NMR spectra.

<p>1a: GD 15 urine samples (PLS-DA, A = 2, R2 = 94.8%, Q2 = 0.613); 1b: GD 21 plasma samples (PCA, A = 4, R2 = 72.5%); 1c: GD21 liver aqueous extract samples (PCA, A = 3, R2 = 61.6%); 1d: GD21 brain aqueous extract samples (PCA, A = 4, R2 = 72.8%). Each dot represents an observation (animal), projected onto first (horizontal axis) and second (vertical axis) PLS-DA or PCA variables. Control group is shown with black squares and the group exposed to eight pesticides widely used in Brittany (France) in 2004 (acetochlor, bromoxynil, carbofuran, chlormequat, ethephon, fenpropimorph, glyphosate, imidacloprid) is shown with red circles. The black ellipse determines the 95% confidence interval, which is drawn using Hotelling’s T2 statistic.</p

Liver fatty acids for which the signals were significantly different between dams from the exposed and control groups (using the Kruskal Wallis test, p-value<0.05).

<p>Liver fatty acids for which the signals were significantly different between dams from the exposed and control groups (using the Kruskal Wallis test, p-value<0.05).</p