Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Chlordecone is a persistent organochlorine pesticide that was used in the French West Indies until the early 1990s for banana weevil borer control. Human exposure to this chemical in this area still occurs nowadays due to consumption of contaminated food. Although adverse effects on neurodevelopment, including tremors and memory deficits, have been documented in experimental studies conducted with rodents exposed during the gestational and neonatal periods, no study has been conducted yet to determine if chlordecone alters child development. This study examines the relation of gestational and postnatal exposure to chlordecone to infant development at 18 months of age in a birth-cohort of Guadeloupean children. In a prospective longitudinal study conducted in Guadeloupe (Timoun mother-child cohort study), exposure to chlordecone was measured at birth from an umbilical cord blood sample (n=141) and from a breast milk sample collected at 3 months postpartum (n=75). Toddlers were assessed using an adapted version of the Ages and Stages Questionnaire. Higher chlordecone concentrations in cord blood were associated with poorer fine motor scores. When analyses were conducted separately for boys and girls, this effect was only observed among boys. These results suggest that prenatal exposure to chlordecone is associated with specific impairments in fine motor function in boys, and add to the growing evidence that exposure to organochlorine pesticides early in life impairs child development.
ISSN: 0161-813X

hal-00875907
https://hal.archives-ouvertes.fr/hal-00875907
PUBMED : 23376090
DOI : 10.1016/j.neuro.2013.01.007

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (β=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (β=-0.14, p=0.07), and longer processing speed (β=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
ISSN: 0013-9351

hal-00875939
https://hal.archives-ouvertes.fr/hal-00875939
DOI : 10.1016/j.envres.2012.07.006
PUBMED : 22910562

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01257867
http://hal.upmc.fr/hal-01257867
http://hal.upmc.fr/hal-01257867/document
http://hal.upmc.fr/hal-01257867/file/journal.pone.0145369.pdf
DOI : 10.1371/journal.pone.0145369