1. Bale TL. 2015. Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 16: 332–344. [Medline] [CrossRef]
2. Ben Maamar M, Beck D, Nilsson EE, Kubsad D, Skinner MK. 2021. Epigenome-wide association study for glyphosate induced transgenerational
sperm DNA methylation and histone retention epigenetic biomarkers for disease. Epigenetics 16: 1150–1167. [Medline] [CrossRef]
3. Collotta M, Bertazzi PA, Bollati V. 2013. Epigenetics and pesticides. Toxicology 307: 35–41. [Medline] [CrossRef]
4. Costas-Ferreira C, Faro LRF. 2021. Neurotoxic effects of neonicotinoids on mammals: What is here beyond the activation of nicotinic acetylcholine
receptors? —A systematic review. Int J Mol Sci 22: 8413. [Medline] [CrossRef]
5. Fitz-James MH, Cavalli G. 2022. Molecular mechanisms of transgenerational epigenetic inheritance. Nat Rev Genet 23: 325–341. [Medline]
[CrossRef]
6. Food and Agriculture Organization of the United Nations. 2016. FAO Specifications and Evaluations for Agricultural Pesticide Clothianidin. https://
www.fao.org/3/ca5099en/ca5099en.pdf [accessed on January 26, 2023].
7. Hansen MB. 2003. The enteric nervous system III: a target for pharmacological treatment. Pharmacol Toxicol 93: 1–13. [Medline] [CrossRef]
8. Hartman C, Legoff L, Capriati M, Lecuyer G, Kernanec PY, Tevosian S, D’Cruz SC, Smagulova F. 2021. Epigenetic effects promoted by neonicotinoid
thiacloprid exposure. Front Cell Dev Biol 9: 691060. [Medline] [CrossRef]
9. Hirano T, Yanai S, Takada T, Yoneda N, Omotehara T, Kubota N, Minami K, Yamamoto A, Mantani Y, Yokoyama T, Kitagawa H, Hoshi N. 2018.
NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a
novel environment. Toxicol Lett 282: 57–63. [Medline] [CrossRef]
10. Hirano T, Yanai S, Omotehara T, Hashimoto R, Umemura Y, Kubota N, Minami K, Nagahara D, Matsuo E, Aihara Y, Shinohara R, Furuyashiki T,
Mantani Y, Yokoyama T, Kitagawa H, Hoshi N. 2015. The combined effect of clothianidin and environmental stress on the behavioral and reproductive
J. Vet. Med. Sci. 85(9): 1023–1029, 2023
1027
A SHODA ET AL.
function in male mice. J Vet Med Sci 77: 1207–1215. [Medline] [CrossRef]
11. Hirano T, Miyata Y, Kubo S, Ohno S, Onaru K, Maeda M, Kitauchi S, Nishi M, Tabuchi Y, Ikenaka Y, Ichise T, Nakayama SMM, Ishizuka M, Arizono
K, Takahashi K, Kato K, Mantani Y, Yokoyama T, Hoshi N. 2021. Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid
pesticide clothianidin in male mice. Toxicol Lett 342: 95–103. [Medline] [CrossRef]
12. Hogg S. 1996. A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54: 21–30.
[Medline] [CrossRef]
13. Hoshi N, Hirano T, Omotehara T, Tokumoto J, Umemura Y, Mantani Y, Tanida T, Warita K, Tabuchi Y, Yokoyama T, Kitagawa H. 2014. Insight into
the mechanism of reproductive dysfunction caused by neonicotinoid pesticides. Biol Pharm Bull 37: 1439–1443. [Medline] [CrossRef]
14. Hu W, Wang G, He B, Hu S, Luo H, Wen Y, Chen L, Wang H. 2020. Effects of prenatal nicotine exposure on hepatic glucose and lipid metabolism in
offspring rats and its hereditability. Toxicology 432: 152378. [Medline] [CrossRef]
15. Ichikawa G, Kuribayashi R, Ikenaka Y, Ichise T, Nakayama SMM, Ishizuka M, Taira K, Fujioka K, Sairenchi T, Kobashi G, Bonmatin JM, Yoshihara
S. 2019. LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth. PLoS One 14: e0219208. [Medline] [CrossRef]
16. Ikenaka Y, Miyabara Y, Ichise T, Nakayama S, Nimako C, Ishizuka M, Tohyama C. 2019. Exposures of children to neonicotinoids in pine wilt disease
control areas. Environ Toxicol Chem 38: 71–79. [Medline] [CrossRef]
17. Jirtle RL, Skinner MK. 2007. Environmental epigenomics and disease susceptibility. Nat Rev Genet 8: 253–262. [Medline] [CrossRef]
18. Kimura-Kuroda J, Komuta Y, Kuroda Y, Hayashi M, Kawano H. 2012. Nicotine-like effects of the neonicotinoid insecticides acetamiprid and
imidacloprid on cerebellar neurons from neonatal rats. PLoS One 7: e32432. [Medline] [CrossRef]
19. Kitauchi S, Maeda M, Hirano T, Ikenaka Y, Nishi M, Shoda A, Murata M, Mantani Y, Yokoyama T, Tabuchi Y, Hoshi N. 2021. Effects of in utero and
lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid clothianidin on the reproductive organs of female
mice. J Vet Med Sci 83: 746–753. [Medline] [CrossRef]
20. Kubsad D, Nilsson EE, King SE, Sadler-Riggleman I, Beck D, Skinner MK. 2019. Assessment of glyphosate induced epigenetic transgenerational
inheritance of pathologies and sperm epimutations: generational toxicology. Sci Rep 9: 6372. [Medline] [CrossRef]
21. Li G, Chang H, Xia W, Mao Z, Li Y, Xu S. 2014. F0 maternal BPA exposure induced glucose intolerance of F2 generation through DNA methylation
change in Gck. Toxicol Lett 228: 192–199. [Medline] [CrossRef]
22. Li Z, Hao MM, Van den Haute C, Baekelandt V, Boesmans W, Vanden Berghe P. 2019. Regional complexity in enteric neuron wiring reflects diversity
of motility patterns in the mouse large intestine. eLife 8: e42914. [Medline] [CrossRef]
23. Maeda M, Yokoyama T, Kitauchi S, Hirano T, Mantani Y, Tabuchi Y, Hoshi N. 2021. Influence of acute exposure to a low dose of systemic insecticide
fipronil on locomotor activity and emotional behavior in adult male mice. J Vet Med Sci 83: 344–348. [Medline] [CrossRef]
24. Maeda M, Kitauchi S, Hirano T, Ikenaka Y, Nishi M, Shoda A, Murata M, Mantani Y, Tabuchi Y, Yokoyama T, Hoshi N. 2021. Fetal and lactational
exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different
behavioral abnormalities at the developmental stages in male mice. J Vet Med Sci 83: 542–548. [Medline] [CrossRef]
25. Mandl P, Kiss JP. 2007. Role of presynaptic nicotinic acetylcholine receptors in the regulation of gastrointestinal motility. Brain Res Bull 72: 194–200.
[Medline] [CrossRef]
26. Meaney MJ. 2001. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev
Neurosci 24: 1161–1192. [Medline] [CrossRef]
27. Murata M, Shoda A, Kimura M, Hara Y, Yonoichi S, Ishida Y, Mantani Y, Yokoyama T, Matsuo E, Hirano T, Hoshi N. 2023. Next-generation effects
of fetal and lactational exposure to the neonicotinoid pesticide clothianidin on the immune system and gut microbiota. J Vet Med Sci 85: 434–442.
[Medline] [CrossRef]
28. Nilsson EE, Ben Maamar M, Skinner MK. 2022. Role of epigenetic transgenerational inheritance in generational toxicology. Environ Epigenet 8:
dvac001. [Medline] [CrossRef]
29. Nishi M, Sugio S, Hirano T, Kato D, Wake H, Shoda A, Murata M, Ikenaka Y, Tabuchi Y, Mantani Y, Yokoyama T, Hoshi N. 2022. Elucidation of the
neurological effects of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) using two-photon microscopy in vivo imaging. J Vet
Med Sci 84: 585–592. [Medline] [CrossRef]
30. Ohno S, Ikenaka Y, Onaru K, Kubo S, Sakata N, Hirano T, Mantani Y, Yokoyama T, Takahashi K, Kato K, Arizono K, Ichise T, Nakayama SMM,
Ishizuka M, Hoshi N. 2020. Quantitative elucidation of maternal-to-fetal transfer of neonicotinoid pesticide clothianidin and its metabolites in mice.
Toxicol Lett 322: 32–38. [Medline] [CrossRef]
31. Onaru K, Ohno S, Kubo S, Nakanishi S, Hirano T, Mantani Y, Yokoyama T, Hoshi N. 2020. Immunotoxicity evaluation by subchronic oral
administration of clothianidin in Sprague-Dawley rats. J Vet Med Sci 82: 360–372. [Medline] [CrossRef]
32. Oya N, Ito Y, Ebara T, Kato S, Ueyama J, Aoi A, Nomasa K, Sato H, Matsuki T, Sugiura-Ogasawara M, Saitoh S, Kamijima M. 2021. Cumulative
exposure assessment of neonicotinoids and an investigation into their intake-related factors in young children in Japan. Sci Total Environ 750: 141630.
[Medline] [CrossRef]
33. Renz H, Brandtzaeg P, Hornef M. 2011. The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nat Rev
Immunol 12: 9–23. [Medline] [CrossRef]
34. Rodgers AB, Morgan CP, Leu NA, Bale TL. 2015. Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal
stress. Proc Natl Acad Sci USA 112: 13699–13704. [Medline] [CrossRef]
35. Shoda A, Nishi M, Murata M, Mantani Y, Yokoyama T, Hirano T, Ikenaka Y, Hoshi N. 2023. Quantitative elucidation of the transfer of the neonicotinoid
pesticide clothianidin to the breast milk in mice. Toxicol Lett 373: 33–40. [Medline] [CrossRef]
36. Shoda A, Murata M, Kimura M, Hara Y, Yonoichi S, Ishida Y, Mantani Y, Yokoyama T, Hirano T, Ikenaka Y, Tabuchi Y, Hoshi N. 2023. Developmental
stage-specific exposure and neurotoxicity evaluation of low-dose clothianidin during neuronal circuit formation. J Vet Med Sci 85: 486–496. [Medline]
[CrossRef]
37. Sun Q, Xiao X, Kim Y, Kim D, Yoon KS, Clark JM, Park Y. 2016. Imidacloprid promotes high fat diet-induced adiposity and insulin resistance in male
C57BL/6J mice. J Agric Food Chem 64: 9293–9306. [Medline] [CrossRef]
38. Sun Q, Qi W, Xiao X, Yang SH, Kim D, Yoon KS, Clark JM, Park Y. 2017. Imidacloprid promotes high fat diet-induced adiposity in female C57BL/6J
mice and enhances adipogenesis in 3T3-L1 adipocytes via the AMPKα-mediated pathway. J Agric Food Chem 65: 6572–6581. [Medline] [CrossRef]
39. Szyf M. 2007. The dynamic epigenome and its implications in toxicology. Toxicol Sci 100: 7–23. [Medline] [CrossRef]
40. Szyf M, Weaver I, Meaney M. 2007. Maternal care, the epigenome and phenotypic differences in behavior. Reprod Toxicol 24: 9–19. [Medline]
[CrossRef]
41. Tanaka T. 2012. Effects of maternal clothianidin exposure on behavioral development in F1 generation mice. Toxicol Ind Health 28: 697–707.
[Medline] [CrossRef]
42. Tanaka T. 2012. Reproductive and neurobehavioral effects of clothianidin administered to mice in the diet. Birth Defects Res B Dev Reprod Toxicol
J. Vet. Med. Sci. 85(9): 1023–1029, 2023
1028
TRANSGENERATIONAL NEUROTOXICITY OF CLOTHIANIDIN
95: 151–159. [Medline] [CrossRef]
43. Tokumoto J, Danjo M, Kobayashi Y, Kinoshita K, Omotehara T, Tatsumi A, Hashiguchi M, Sekijima T, Kamisoyama H, Yokoyama T, Kitagawa H,
Hoshi N. 2013. Effects of exposure to clothianidin on the reproductive system of male quails. J Vet Med Sci 75: 755–760. [Medline] [CrossRef]
44. Tomizawa M, Casida JE. 2005. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol 45: 247–268.
[Medline] [CrossRef]
45. Ueyama J, Harada KH, Koizumi A, Sugiura Y, Kondo T, Saito I, Kamijima M. 2015. Temporal levels of urinary neonicotinoid and dialkylphosphate
concentrations in Japanese women between 1994 and 2011. Environ Sci Technol 49: 14522–14528. [Medline] [CrossRef]
46. Uneme H, Konobe M, Akayama A, Yokota T, Mizuta K. 2006. Discovery and development of a novel insecticide ‘clothianidin’, Sumitomo Kagaku 2.
pp. 1–14. https://www.sumitomo-chem.co.jp/english/rd/report/files/docs/20060202_h6t.pdf [accessed on January 26, 2023].
47. Wang W, Ito T, Otsuka S, Nansai H, Abe K, Nakao Y, Ohgane J, Yoneda M, Sone H. 2021. Epigenetic effects of insecticides on early differentiation
of mouse embryonic stem cells. Toxicol In Vitro 75: 105174. [Medline] [CrossRef]
48. World Health Organization, United Nations Environment Programme (WHO-UNEP). 2012. State of the science of endocrine disrupting chemicals
(Bergman A, Heindel JJ, Jobling S, Kidd KA, Zoeller RT eds.), Geneva.
49. Xin F, Susiarjo M, Bartolomei MS. 2015. Multigenerational and transgenerational effects of endocrine disrupting chemicals: A role for altered
epigenetic regulation? Semin Cell Dev Biol 43: 66–75. [Medline] [CrossRef]
50. Yanai S, Hirano T, Omotehara T, Takada T, Yoneda N, Kubota N, Yamamoto A, Mantani Y, Yokoyama T, Kitagawa H, Hoshi N. 2017. Prenatal and
early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice. J Vet Med Sci 79: 1196–1203. [Medline]
[CrossRef]
J. Vet. Med. Sci. 85(9): 1023–1029, 2023
1029
...