title: Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos.
abstract: The complexity of the neuroendocrine level of investigation requires the assessment of behavioral patterns that extend beyond the reproductive functions, which are age- and sex-specific in rodents, described by defined clusters of behavioral items regulated by genetic, hormonal, and epigenetic factors. The study of social behavior in laboratory rodents reveals sex-dimorphic effects of environmental chemicals that may be undetected either by a traditional neurotoxicological approach or referring to the classical definition of endocrine disrupting chemicals. Here we review data on the neurobehavioral effects of developmental exposure to the non-persistent organophosphorus insecticide chlorpyrifos, whose neurotoxic activity at low doses is currently a matter of concern for children's health. In mice exposed to chlorpyrifos in utero and/or in early development social/emotional responses are differently affected in the two sexes in parallel with sex-dependent interference on hypothalamic neuroendocrine pathways regulating social behaviors (vasopressin, oxytocin, and steroid regulated systems). Through the analysis of complex sex-dimorphic behavioral patterns we show that neurotoxic and endocrine disrupting activities of CPF overlap. This widely diffused organophosphorus pesticide might thus be considered as a neuroendocrine disruptor possibly representing a risk factor for sex-biased neurodevelopmental disorders in children.
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Dept. Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Venerosi
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Dept. Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. Electronic address: laura.ricceri@iss.it.
authors.forename: L
authors.initials: L
authors.lastname: Ricceri
authors.affiliation: Section of Food and Veterinary Toxicology, Dept. Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tait
authors.affiliation: Section of Neurotoxicology and Neuroendocrinology, Dept. Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Calamandrei
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D004390:Chlorpyrifos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018570:Risk Assessment; D012727:Sex Characteristics; D012737:Sex Factors; D012919:Social Behavior
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004390:Chlorpyrifos