Early exposure to low doses of atrazine affects behavior in juvenile and adult CD1 mice

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 100g/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.