Toxicology : The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

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  • HIRANO Tetsushi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • YANAI Shogo
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • OMOTEHARA Takuya
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • HASHIMOTO Rie
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • UMEMURA Yuria
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • KUBOTA Naoto
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MINAMI Kiichi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • NAGAHARA Daichi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • MATSUO Eiko
    Laboratory of Microbiology and Immunology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • AIHARA Yoshiko
    Laboratory of Food and Nutritional Chemistry, Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • SHINOHARA Ryota
    Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Kyoto 606–8501, Japan
  • FURUYASHIKI Tomoyuki
    Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Kobe University, Kobe, Hyogo, 650–0017, Japan
  • MANTANI Youhei
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • YOKOYAMA Toshifumi
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • KITAGAWA Hiroshi
    Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan
  • HOSHI Nobuhiko
    Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657–8501, Japan

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  • The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

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Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure.

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