title: The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice.
abstract: 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.
authors.affiliation: Laboratory of Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Hirano
authors.forename: Shogo
authors.initials: S
authors.lastname: Yanai
authors.forename: Takuya
authors.initials: T
authors.lastname: Omotehara
authors.forename: Rie
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yuria
authors.initials: Y
authors.lastname: Umemura
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Kiichi
authors.initials: K
authors.lastname: Minami
authors.forename: Daichi
authors.initials: D
authors.lastname: Nagahara
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsuo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Aihara
authors.forename: Ryota
authors.initials: R
authors.lastname: Shinohara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Youhei
authors.initials: Y
authors.lastname: Mantani
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D000073943:Neonicotinoids; D009929:Organ Size / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D011897:Random Allocation; D012098:Reproduction / Q000187:drug effects*; D013312:Stress, Physiological; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013844:Thiazoles / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D006146:Guanidines; D000073943:Neonicotinoids; D010575:Pesticides; D013844:Thiazoles; C480342:clothianidin