Exposure to bisphenol A or its phenolic analogs during early life induces different types of anxiety-like behaviors after maturity in male mice

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  • Sasaki Takahiro
    Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University
  • Saito Hirokatsu
    Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
  • Furukawa Yusuke
    Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
  • Tominaga Takashi
    Laboratory for Neural Circuit Systems, Institute of Neuroscience, Tokushima Bunri University
  • Kitajima Satoshi
    Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
  • Kanno Jun
    Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
  • Tanemura Kentaro
    Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University

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Abstract

<p>Products used in daily life contain multiple chemicals capable of inducing endocrine disruption in animals, including humans. One such typical substance is bisphenol A (BPA). BPA has been widely used in epoxy resins and polycarbonate plastics and can exert several adverse effects. Furthermore, given their structural similarity to BPA, phenolic analogs of BPA, i.e., synthetic phenolic antioxidants (SPAs), are considered to exhibit similar toxicity; however, the effects of early SPA exposure on the adult central nervous system remain poorly clarified. In the present study, we aimed to evaluate and compare the neurobehavioral effects of early life exposure to BPA and two selected SPAs, 4,4'-butylidenebis (6-tert-butyl-m-cresol) (BB) and 2,2'-methylenebis (6-tert-butyl-p-cresol) (MB). We exposed mice to low levels of these chemicals through drinking water during prenatal and postnatal periods. Subsequently, we examined the adverse effects of these chemicals on the central nervous system using a mouse behavioral test battery, comprising the open field test, light/dark transition test, elevated plus-maze test, contextual/cued fear conditioning test, and prepulse inhibition test, at 12-13 weeks old. Based on the behavioral analysis, SPAs, like BPA, may cause affective disorders even at low doses, although qualitative differences were noted in anxiety-related behaviors. In conclusion, our findings could be valuable for clarifying the potential adverse developmental risks of SPA exposure in early life.</p>

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