Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children. OBJECTIVES: We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort. METHODS: In 2002-2006, the PELAGIE mother-child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks' gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children-4th edition (WISC-IV) was administered at 6 years to evaluate cognitive function (n=231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used. RESULTS: WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate metabolites (DE) (5.5; 95% CI: 0.8, 10.3 for extgreater 13.2 nmol/L versus extlessLOQ), while WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (-3.6; 95% CI: -7.8, -0.6 for extgreater 11.1 nmol/L versus extlessLOD). CONCLUSION: This study found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the higher population's socioeconomic status than in previous studies though other causal and non-causal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure
Environmental Health Perspectives

hal-01207282
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207282
DOI : 10.1289/ehp.1409472
PUBMED : 26394442

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Herbicides are generally the most extensively used of the pesticides applied to agricultural crops. However, the literature contains little evidence useful in assessing the potential sources of the general population's exposure to herbicides, including by residential proximity to crops. The objective of this study was to take advantage of data from the PELAGIE mother-child cohort to identify the main determinants of the body burden of exposure to the chloroacetanilide and triazine herbicides commonly used on corn crops in Brittany, France, before 2006. Urine samples from a randomly selected subcohort of women in the first trimester of pregnancy (n=579) were assayed for herbicide metabolites. The residential exposure resulting from proximity to corn crops was assessed with satellite-image-based scores combined with meteorological data. Data on diet, drinking tap water (from the public water supply), occupations, and household herbicide use were collected by questionnaires. Herbicides were quantified in 5.3% to 39.7% of urine samples. Alachlor and acetochlor were found most frequently in the urine of women living in rural areas. The presence of dealkylated triazine metabolites in urine samples was positively associated with residential proximity to corn crops (OR=1.38, 95% CI: 1.05-1.80). Urinary metabolites of both atrazine and dealkylated triazine were correlated with tap water consumption (OR=2.94, 1.09-7.90, and OR=1.82, 1.10-3.03, respectively); hydroxylated triazine metabolites were correlated with fish intake (OR=1.48, 1.09-1.99). This study reinforces previous results that suggest that environmental contamination resulting from agricultural activities may contribute to the general population's exposure to herbicides.
Environment International

hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842
https://hal.archives-ouvertes.fr/hal-00966842/document
DOI : 10.1016/j.envint.2013.10.010
PUBMED : 24246238

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.
ISSN: 0305-1048

inserm-00716879
http://www.hal.inserm.fr/inserm-00716879
http://www.hal.inserm.fr/inserm-00716879/document
http://www.hal.inserm.fr/inserm-00716879/file/nar.gks595.full.pdf
DOI : 10.1093/nar/gks595

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend = 0.04 and P-trend < 0.01, respectively) and with working memory scores (P-trend = 0.05 and P-trend < 0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6 years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance
ISSN: 0160-4120

hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01162374/file/Pyrethroid%20insecticide%20exposure.pdf
DOI : 10.1016/j.envint.2015.05.009