{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:12:39Z","timestamp":1783746759918,"version":"3.55.0"},"reference-count":46,"publisher":"Japanese Society of Veterinary Science","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Vet. Med. Sci.","The Journal of Veterinary Medical Science"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1292\/jvms.25-0497","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T22:09:51Z","timestamp":1778710191000},"page":"1061-1071","source":"Crossref","is-referenced-by-count":0,"title":["Developmental and behavioral effects of fetal and neonatal exposure to the          phenylpyrazole pesticide fipronil in mice"],"prefix":"10.1292","volume":"88","author":[{"given":"Ayano","family":"YOSHIMOTO","sequence":"first","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika","family":"NUNOBIKI","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"ITO","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"YONOICHI","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"HARA","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"ISHIDA","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhei","family":"MANTANI","sequence":"additional","affiliation":[{"name":"Laboratory of Histophysiology, Department of Animal              Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"YOKOYAMA","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"HIRANO","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of              Toyama, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"IKENAKA","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Department of Environmental              Veterinary Sciences, Faculty of Veterinary Medicine Hokkaido University, Hokkaido,              Japan"},{"name":"Translational Research Unit, Veterinary Teaching              Hospital, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido,              Japan"},{"name":"One Health Research Center, Hokkaido University,              Hokkaido, Japan"},{"name":"Water Research Group, Unit for Environmental Sciences              and Management, North-West University, Potchefstroom, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"HOSHI","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Molecular Morphology, Department              of Animal Science, Graduate School of Agricultural Science, Kobe University, Hyogo,              Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"122","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Abdel-Daim              MM, Abdeen              A. 2018.            Protective effects of rosuvastatin and vitamin E against            fipronil-mediated oxidative damage and apoptosis in rat liver and          kidney. <i>Food Chem Toxicol<\/i>          114: 69\u201377.","DOI":"10.1016\/j.fct.2018.01.055"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Aldayel              TS,                Abdel-Rahman              HG, Gad                El-Hak              HN,                Abdelrazek              HMA, Mohamed              RM, El-Sayed              RM. 2021.            Assessment of modulatory activity of Uncaria tomentosa extract against            fipronil immunotoxicity in male rats. <i>Ecotoxicol Environ              Saf<\/i>          224: 112674.","DOI":"10.1016\/j.ecoenv.2021.112674"},{"key":"3","unstructured":"3. Alva-S\u00e1nchez              C,                Pacheco-Rosado              J,                Fregoso-Aguilar              T, Villanueva              I. 2012.            The long-term regulation of food intake and body weight depends on the            availability of thyroid hormones in the brain.              <i>Neuroendocrinol Lett<\/i>          33: 703\u2013708."},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Alvarez              EO. 2009.            The role of histamine on cognition. <i>Behav              Brain Res<\/i>          199: 183\u2013189.","DOI":"10.1016\/j.bbr.2008.12.010"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Auger              CJ,                Forbes-Lorman              RM. 2008.            Progestin receptor-mediated reduction of anxiety-like behavior in male            rats. <i>PLoS One<\/i>          3: e3606.","DOI":"10.1371\/journal.pone.0003606"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Boyle              N, Betts              S, Lu              H. 2024.            Monoaminergic modulation of learning and cognitive function in the            prefrontal cortex. <i>Brain Sci<\/i>          14: 902.","DOI":"10.3390\/brainsci14090902"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Bychowski              ME, Auger              CJ. 2012.            Progesterone impairs social recognition in male rats.              <i>Horm Behav<\/i>          61: 598\u2013604.","DOI":"10.1016\/j.yhbeh.2012.02.009"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Chang              YN, Tsai              TH. 2020.            Preclinical transplacental transfer and pharmacokinetics of fipronil in            rats. <i>Drug Metab Dispos<\/i>          48: 886\u2013893.","DOI":"10.1124\/dmd.120.000088"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Charnley              G, Putzrath              RM. 2001.            Children\u2019s health, susceptibility, and regulatory approaches to reducing            risks from chemical carcinogens. <i>Environ Health              Perspect<\/i>          109: 187\u2013192.","DOI":"10.1289\/ehp.01109187"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Cheng              J, Ju              XL, Chen              XY, Liu              GY. 2009.            Homology modeling of human \u03b1 1 \u03b2 2 \u03b3 2 and house fly \u03b2 3 GABA receptor            channels and Surflex-docking of fipronil. <i>J Mol              Model<\/i>          15: 1145\u20131153.","DOI":"10.1007\/s00894-009-0477-2"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Cravedi              JP, Delous              G, Zalko              D, Vigui\u00e9              C, Debrauwer              L. 2013.            Disposition of fipronil in rats.              <i>Chemosphere<\/i>          93: 2276\u20132283.","DOI":"10.1016\/j.chemosphere.2013.07.083"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Eskenazi              B, Rosas              LG, Marks              AR, Bradman              A, Harley              K, Holland              N, Johnson              C, Fenster              L, Barr              DB. 2008.            Pesticide toxicity and the developing brain.              <i>Basic Clin Pharmacol Toxicol<\/i>          102: 228\u2013236.","DOI":"10.1111\/j.1742-7843.2007.00171.x"},{"key":"13","unstructured":"13. European Food Safety            Authority.          2013. EFSA assesses risks to bees from fipronil. https:\/\/www.efsa.europa.eu\/en\/press\/news\/130527 [accessed on January 10,          2020]."},{"key":"14","unstructured":"14. Food Safety Commission of            Japan. 2016. Risk Assessment Report. Fipronil (pesticides and          veterinary medicinal products) (in Japanese)."},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Frye              CA, Lembo              VF, Walf              AA. 2021.            Progesterone\u2019s effects on cognitive performance of male mice are            independent of progestin receptors but relate to increases in GABA<sub>A<\/sub> activity            in the hippocampus and cortex. <i>Front Endocrinol              (Lausanne)<\/i>          11: 552805.","DOI":"10.3389\/fendo.2020.552805"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Fujibayashi              M, Kamiya              T, Takagaki              K, Moritani              T. 2008.            Activation of autonomic nervous system activity by the oral ingestion of            GABA. <i>J Jpn Soc Nutr Food Sci<\/i>          61: 129\u2013133.","DOI":"10.4327\/jsnfs.61.129"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Godinho              AF, de Oliveira                Souza              AC, Carvalho              CC, Horta              DF, De Fraia              D, Anselmo              F, Chaguri              JL, Faria              CA. 2016.            Memory impairment due to fipronil pesticide exposure occurs at the              GABA<sub>A<\/sub> receptor level, in rats. <i>Physiol              Behav<\/i>          165: 28\u201334.","DOI":"10.1016\/j.physbeh.2016.06.035"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Hainzl              D, Cole              LM, Casida              JE. 1998.            Mechanisms for selective toxicity of fipronil insecticide and its sulfone            metabolite and desulfinyl photoproduct. <i>Chem Res              Toxicol<\/i>          11: 1529\u20131535.","DOI":"10.1021\/tx980157t"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Hefft              S, Kraushaar              U, Geiger              JRP, Jonas              P. 2002.            Presynaptic short-term depression is maintained during regulation of            transmitter release at a GABAergic synapse in rat hippocampus.              <i>J Physiol<\/i>          539: 201\u2013208.","DOI":"10.1113\/jphysiol.2001.013455"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. 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. <i>Toxicol Lett<\/i>          282: 57\u201363.","DOI":"10.1016\/j.toxlet.2017.10.010"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Kim              YA, Yoon              YS, Kim              HS, Jeon              SJ, Cole              E, Lee              J, Kho              Y, Cho              YH. 2019.            Distribution of fipronil in humans, and adverse health outcomes of in            utero fipronil sulfone exposure in newborns. <i>Int J Hyg              Environ Health<\/i>          222: 524\u2013532.","DOI":"10.1016\/j.ijheh.2019.01.009"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Kitaoka              S, Hatogai              J, Iimura              R, Yamamoto              Y, Oba              K, Nakai              M, Kusunoki              Y, Ochiai              W, Sugiyama              K. 2018.            Relationship between low midazolam metabolism by cytochrome P450 3A in            mice and the high incidence of birth defects. <i>J Toxicol              Sci<\/i>          43: 65\u201374.","DOI":"10.2131\/jts.43.65"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Korte              SM. 2001.            Corticosteroids in relation to fear, anxiety and            psychopathology. <i>Neurosci Biobehav Rev<\/i>          25: 117\u2013142.","DOI":"10.1016\/S0149-7634(01)00002-1"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Kubo              S, Hirano              T, Miyata              Y, Ohno              S, Onaru              K, Ikenaka              Y, Nakayama              SMM, Ishizuka              M, Mantani              Y, Yokoyama              T, Hoshi              N. 2022.            Sex-specific behavioral effects of acute exposure to the neonicotinoid            clothianidin in mice. <i>Toxicol Appl            Pharmacol<\/i>          456: 116283.","DOI":"10.1016\/j.taap.2022.116283"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Leghait              J, Gayrard              V,                Picard-Hagen              N, Camp              M, Perdu              E, Toutain              PL, Vigui\u00e9              C. 2009.            Fipronil-induced disruption of thyroid function in rats is mediated by            increased total and free thyroxine clearances concomitantly to increased activity of            hepatic enzymes. <i>Toxicology<\/i>          255: 38\u201344.","DOI":"10.1016\/j.tox.2008.09.026"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Le Patourel.          2000. Secondary transmission of fipronil toxicity between            Oriental cockroaches Blatta orientalis L in arenas. <i>Pest              Manag Sci<\/i>          56: 732\u2013736.","DOI":"10.1002\/1526-4998(200009)56:9<732::AID-PS206>3.0.CO;2-F"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Li              P, Abd El-Aty              AM, Jiang              H, Shen              J, Wang              Z, Wen              K, Li              J, Wang              S, Wang              J, Hammock              BD, Jin              M. 2024.            Immunoassays and emerging analytical techniques of fipronil and its            metabolites for food safety: a review. <i>J Agric Food              Chem<\/i>          72: 2059\u20132076.","DOI":"10.1021\/acs.jafc.3c07428"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. 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. <i>J Vet Med Sci<\/i>          83: 344\u2013348.","DOI":"10.1292\/jvms.20-0551"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. McMahen              RL, Strynar              MJ, Dagnino              S, Herr              DW, Moser              VC,                Garantziotis              S, Andersen              EM, Freeborn              DL, McMillan              L, Lindstrom              AB. 2015.            Identification of fipronil metabolites by time-of-flight mass            spectrometry for application in a human exposure study.              <i>Environ Int<\/i>          78: 16\u201323.","DOI":"10.1016\/j.envint.2015.01.016"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Nakanishi              K, Yokomizo              H, Hayashi              TI. 2018.            Were the sharp declines of dragonfly populations in the 1990s in Japan            caused by fipronil and imidacloprid? An analysis of Hill\u2019s causality for the case of              <i>Sympetrum frequens<\/i>. <i>Environ Sci              Pollut Res Int<\/i>          25: 35352\u201335364.","DOI":"10.1007\/s11356-018-3440-x"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Ohi              M, Dalsenter              PR, Andrade              AJM,                Nascimento              AJ. 2004.            Reproductive adverse effects of fipronil in Wistar rats.              <i>Toxicol Lett<\/i>          146: 121\u2013127.","DOI":"10.1016\/j.toxlet.2003.08.008"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. 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.              <i>Toxicol Lett<\/i>          322: 32\u201338.","DOI":"10.1016\/j.toxlet.2020.01.003"},{"key":"33","unstructured":"33. Pesticide Resistance Action            Committee.          2019. Pesticide Mode of Action. Version 1.0. https:\/\/irac-online.org\/documents\/tutorial-on-moa-mechanisms [accessed on          January 12, 2025]."},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Roberts              JR, Dawley              EH, Reigart              JR. 2019.            Children\u2019s low-level pesticide exposure and associations with autism and            ADHD: a review. <i>Pediatr Res<\/i>          85: 234\u2013241.","DOI":"10.1038\/s41390-018-0200-z"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Schlenk              D, Huggett              DB, Allgood              J, Bennett              E, Rimoldi              J, Beeler              AB, Block              D, Holder              AW, Hovinga              R, Bedient              P. 2001.            Toxicity of fipronil and its degradation products to              <i>Procambarus<\/i> sp.: field and laboratory studies.              <i>Arch Environ Contam Toxicol<\/i>          41: 325\u2013332.","DOI":"10.1007\/s002440010255"},{"key":"36","doi-asserted-by":"crossref","unstructured":"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.              <i>J Vet Med Sci<\/i>          85: 486\u2013496.","DOI":"10.1292\/jvms.22-0570"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. 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. <i>Toxicol              Lett<\/i>          373: 33\u201340.","DOI":"10.1016\/j.toxlet.2022.10.006"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Speranza              L, di Porzio              U, Viggiano              D, de Donato              A, Volpicelli              F. 2021.            Dopamine: the neuromodulator of long-term synaptic plasticity, reward and            movement control. <i>Cells<\/i>          10: 735.","DOI":"10.3390\/cells10040735"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Suzuki              K. 2018.            The developing world of DOHaD. <i>J Dev Orig              Health Dis<\/i>          9: 266\u2013269.","DOI":"10.1017\/S2040174417000691"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Suzuki              T, Hirai              A, Khidkhan              K, Nimako              C, Ichise              T, Takeda              K, Mizukawa              H, Nakayama              SMM, Nomiyama              K, Hoshi              N, Maeda              M, Hirano              T, Sasaoka              K, Sasaki              N, Takiguchi              M, Ishizuka              M, Ikenaka              Y. 2021.            The effects of fipronil on emotional and cognitive behaviors in            mammals. <i>Pestic Biochem Physiol<\/i>          175: 104847.","DOI":"10.1016\/j.pestbp.2021.104847"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Tang              J, Amin                Usmani              K, Hodgson              E, Rose              RL. 2004.            In vitro metabolism of fipronil by human and rat cytochrome P450 and its            interactions with testosterone and diazepam. <i>Chem Biol              Interact<\/i>          147: 319\u2013329.","DOI":"10.1016\/j.cbi.2004.03.002"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Tessari              L, Angriman              M, D\u00edaz-Rom\u00e1n              A, Zhang              J, Conca              A, Cortese              S. 2022.            Association between exposure to pesticides and ADHD or autism spectrum            disorder: a systematic review of the literature. <i>J Atten              Disord<\/i>          26: 48\u201371.","DOI":"10.1177\/1087054720940402"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Toffoletto              S,                Lanzenberger              R, Gingnell              M,                Sundstr\u00f6m-Poromaa              I, Comasco              E. 2014.            Emotional and cognitive functional imaging of estrogen and progesterone            effects in the female human brain: a systematic review.              <i>Psychoneuroendocrinology<\/i>          50: 28\u201352.","DOI":"10.1016\/j.psyneuen.2014.07.025"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Yoshimoto              A, Nunobiki              S, Ito              M, Yonoichi              S, Hara              Y, Ishida              Y, Mantani              Y, Yokoyama              T, Hirano              T, Ikenaka              Y, Hoshi              N. 2025.            Effects of low-dose subchronic exposure to the phenylpyrazole insecticide            fipronil in juvenile mice. <i>J Vet Med            Sci<\/i>          87: 419\u2013425.","DOI":"10.1292\/jvms.24-0531"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Zhang              Q, Wang              X, Wang              Q, Qi              D, Huang              Y, Chen              R, Shan              Y, Fang              W. 2023.            Toxicological effects of fipronil on laying hens and its residue            elimination in eggs. <i>Environ Sci Pollut Res            Int<\/i>          30: 19304\u201319312.","DOI":"10.1007\/s11356-022-23506-7"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Zhao              X, Yeh              JZ, Salgado              VL, Narahashi              T. 2005.            Sulfone metabolite of fipronil blocks \u03b3-aminobutyric acid- and            glutamate-activated chloride channels in mammalian and insect neurons.              <i>J Pharmacol Exp Ther<\/i>          314: 363\u2013373.","DOI":"10.1124\/jpet.104.077891"}],"container-title":["Journal of Veterinary Medical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jvms\/88\/7\/88_25-0497\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:30:20Z","timestamp":1783744220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jvms\/88\/7\/88_25-0497\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1292\/jvms.25-0497","relation":{},"ISSN":["0916-7250","1347-7439"],"issn-type":[{"value":"0916-7250","type":"print"},{"value":"1347-7439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"25-0497"}}