title: Early exposure to low doses of atrazine affects behavior in juvenile and adult CD1 mice.
abstract: Environmental exposure to endocrine disrupting chemicals is receiving increasing attention, with particular regard to distinct periods of development where neuroendocrine circuitries are critical for shaping the mammalian brain. Atrazine (ATZ), a widely used herbicide, has been reported to affect steroid hormones and interfere with pathways critical for sex-specific physiological and behavioral development. Aim of the present study was to evaluate effects of perinatal exposure to environmentally relevant subtoxic doses of ATZ, on neurobehavioral development in mice and investigate possible alterations in steroid hormone metabolism. Neurobehavioral development of female and male mice delivered from CD1 dams, and daily exposed from Gestational Day 14 until Postnatal Day 21 (PND 21) to 1 or 100 μg/kg bw ATZ, was investigated. Specifically, locomotor and exploratory activity, social interactions and cognitive performance were evaluated at PND 16, 31 and 60, respectively. Moreover, general toxicity clinical signs, testicular parameters, rate of testosterone metabolism and aromatase activity in F1 male liver were analyzed at adulthood. Changes in exploratory profile and in affiliative/investigative behavior were observed, revealing a feminization of behavioral profile in ATZ-exposed males. Alteration in learning performance at adulthood was also evident. A limited decreased sperm count and concentration, as well as some slight impairment in hepatic testosterone metabolism and in aromatase activity (slightly but not significantly decreased) were observed in both low and high dose exposed animals. In conclusion developmental exposure to non-toxic, environmentally relevant doses of ATZ can produce subtle functional alterations, detectable in juvenile rodents by a detailed behavioral analysis. Behavioral disturbances appeared mainly related with neurodevelopmental disorder affecting the social domain and the emotional/affective repertoire, although further research is needed to elucidate the mechanism through which the effects are induced.
authors.affiliation: Section of Behavioural Neurosciences, Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Belloni
authors.forename: Francesco
authors.initials: F
authors.lastname: Dessì-Fulgheri
authors.forename: Marco
authors.initials: M
authors.lastname: Zaccaroni
authors.forename: Emma
authors.initials: E
authors.lastname: Di Consiglio
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Angelis
authors.forename: Emanuela
authors.initials: E
authors.lastname: Testai
authors.forename: Michela
authors.initials: M
authors.lastname: Santochirico
authors.forename: Enrico
authors.initials: E
authors.lastname: Alleva
authors.forename: Daniela
authors.initials: D
authors.lastname: Santucci
mesh_terms: D000367:Age Factors; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000008:administration & dosage / Q000633:toxicity*; D007858:Learning / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012919:Social Behavior; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D052244:Endocrine Disruptors; D006540:Herbicides; D013739:Testosterone; D001280:Atrazine