title: Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.
abstract: BACKGROUND
  Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides worldwide. Epidemiological studies on pregnant women and their children suggest a link between in utero CPF exposure and delay in psychomotor and cognitive maturation. A large number of studies in animal models have shown adverse effects of CPF on developing brain and more recently on endocrine targets. Our aim was to determine if developmental exposure to CPF affects social responsiveness and associated molecular neuroendocrine markers at adulthood.
  
  
  METHODS
  Pregnant CD1 outbred mice were fed from gestational day 15 to lactation day 14 with either a CPF-added (equivalent to 6 mg/kg/bw/day during pregnancy) or a standard diet. We then assessed in the offspring the long-term effects of CPF exposure on locomotion, social recognition performances and gene expression levels of selected neurondocrine markers in amygdala and hypothalamus.
  
  
  RESULTS
  No sign of CPF systemic toxicity was detected. CPF induced behavioral alterations in adult offspring of both sexes: CPF-exposed males displayed enhanced investigative response to unfamiliar social stimuli, whereas CPF-exposed females showed a delayed onset of social investigation and lack of reaction to social novelty. In parallel, molecular effects of CPF were sex dimorphic: in males CPF increased expression of estrogen receptor beta in hypothalamus and decreased oxytocin expression in amygdala; CPF increased vasopressin 1a receptor expression in amygdala in both sexes.
  
  
  CONCLUSIONS
  These data indicate that developmental CPF affects mouse social behavior and interferes with development of sex-dimorphic neuroendocrine pathways with potential disruptive effects on neuroendocrine axes homeostasis. The route of exposure selected in our study corresponds to relevant human exposure scenarios, our data thus supports the view that neuroendocrine effects, especially in susceptible time windows, should deserve more attention in risk assessment of OP insecticides.
authors.affiliation: Department Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. aldina.venerosi@iss.it.
authors.forename: Aldina
authors.initials: A
authors.lastname: Venerosi
authors.affiliation: Department Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy. sabrina.tait@iss.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Tait
authors.affiliation: Department Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome, Italy. laura.stecca@ec.europa.eu.
authors.forename: Laura
authors.initials: L
authors.lastname: Stecca
authors.affiliation: Department Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. flavia.chiarotti@iss.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiarotti
authors.affiliation: Department Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. alessiadefelice5@gmail.com.
authors.forename: Alessia
authors.initials: A
authors.lastname: De Felice
authors.affiliation: Department Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy. mariafrancesca.cometa@iss.it.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Cometa
authors.affiliation: Department Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy. mariateresa.volpe@iss.it.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Volpe
authors.affiliation: Department Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. gemma.calamandrei@iss.it.
authors.forename: Gemma
authors.initials: G
authors.lastname: Calamandrei
authors.affiliation: Department Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy. laura.ricceri@iss.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Ricceri
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004390:Chlorpyrifos / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D012919:Social Behavior
chemical_list: D015415:Biomarkers; D007306:Insecticides; D011960:Receptors, Estrogen; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D000110:Acetylcholinesterase; D004390:Chlorpyrifos