Perinatal programming of intestinal homeostasis following exposure to low dose of chlorpyrifos in male rats offspring

Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, PC161

Poster Communications: Perinatal programming of intestinal homeostasis following exposure to low dose of chlorpyrifos in male rats offspring

M. Guibourdenche1,2, H. El Khayat El Sabbouri1, A. Bouzerara3, N. Djekkoun1, H. Khorsi-Cauet1, J. Guibourdenche3, V. Bach1, P. M Anton2, J. Gay-Quéheillard1

1. PériTox, Périnatalité & Risques Toxiques, UMR-I 01 , UPJV, Amiens, France, Amiens, France. 2. Equipe PETALES - EA 7519 - Unité Transformations & Agro-Ressources, UniLaSalle, Beauvais, France. 3. Biologie hormonale, CHU Cochin, Université Paris Descartes, AP-HP, Paris, France.

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OBJECTIVE Perinatal period is characterized by phases of development with high sensitivity to environmental factors. Among the risk factors, pesticide exposure are now recognized to program children’s metabolism and promote the occurrence of obesity or type 2 diabetes. This study purposes the peri-gestational exposure of mothers (animal model: rat) to a low dose of pesticide (chlorpyrifos, CPF). This exposition might increase the occurrence of obesity, associated with metabolic disorders and disturbances of digestive function in male offsprings. METHODS 8 female Wistar rats were exposed to CPF, and 8 female rats to its vehicle (controls) , supplemented or not with inulin. Female rats were exposed to these experimental conditions during a pre-gestational period of 4 months as well as during the gestation and lactation periods. After weaning, 56 male pups were studied at young adulthood (D60), without any treatment during the experiment. Different segments of the digestive tract were studied for histological analysis, metabolic assays, inflammation and intestinal permeability. RESULTS Rats from mothers exposed to CPF have lower birth weights than control pups (p<0.05), but this difference appears to decrease at young adult age (J60). Lipid and glycemic assays did not show significant differences. We noticed a decrease of IGF1 (p<0.01) in animals from CPF-exposed mothers as well as a decrease in leptin plasma levels but not significantly. FITC assays didn’t show any perturbation of the intestinal permeability. LPS and pro inflammatory cytokines assays (IL6, IL1β, TNFα) didn’t show any tissue inflammation. Intergroup comparisons were performed using one-way ANOVA with Bonferroni’s post test was performed using GraphPad Prism version 5.00 for Windows, GraphPad Software, San Diego California USA, www.graphpad.com”. CONCLUSIONS Preliminary results reveal that pups from mothers in contact with a pesticide during the peri-gestational period have developmental disabilities characterized by a lower birth weight, but also a decrease in plasma levels of factors involved in growth and metabolism (IGF1 and leptin). We suggest that the pesticide slows down fetal and postnatal development. This hypothesis remains to be confirmed after analysis of tight junction proteins of the intestinal barrier, other inflammatory markers and morphological alterations of the digestive system.



Where applicable, experiments conform with Society ethical requirements.

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