Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation
Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) have been unintentionally produced and emitted from the lifecycle of products containing brominated flame retardants, such as polybrominated diphenyl ether, which is suspected to cause developmental neurotoxicity (DNT). Although it is pla...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412020317888 |
| _version_ | 1818610006843457536 |
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| author | Eiki Kimura Go Suzuki Naoto Uramaru Toshihiro Endo Fumihiko Maekawa |
| author_facet | Eiki Kimura Go Suzuki Naoto Uramaru Toshihiro Endo Fumihiko Maekawa |
| author_sort | Eiki Kimura |
| collection | DOAJ |
| description | Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) have been unintentionally produced and emitted from the lifecycle of products containing brominated flame retardants, such as polybrominated diphenyl ether, which is suspected to cause developmental neurotoxicity (DNT). Although it is plausible that PBDD/DFs can also induce DNT, information regarding their neurotoxic potential is currently limited. Hence, in the present study, we examined the effects of in utero and lactational exposure to brominated dibenzofurans on infant and adult offspring behavior to understand the mechanism of PBDD/DFs toxicity and detect effective behavioral endpoints in DNT assessment. We analyzed the behavior of mouse offspring born to dams administered 2,3,7,8-tetrabromodibenzofuran (2,3,7,8-TeBDF; dose of 0, 9, or 45 μg/kg) or 2,3,8-tribromodibenzofuran (2,3,8-TrBDF; dose of 0, 75.6, or 378 μg/kg) on gestational day 12.5. In mouse offspring born to dams exposed to 2,3,7,8-TeBDF, the exploratory behavior in a novel environment in adulthood and ultrasonic vocalization (USV) during infancy were significantly reduced. Additionally, AhR-target genes, such as Cyp1a1, were induced in the liver of 2,3,7,8-TeBDF-exposed offspring in a dose-dependent manner. Conversely, no significant changes in the infant and adult behaviors and expression level of AhR-target genes were observed in the 2,3,8-TrBDF-exposed offspring. These results suggest that 2,3,7,8-TeBDF can induce DNT and that the analysis of exploratory behavior in a novel environment and USV may be useful endpoints to assess DNT of dioxin-related substances. |
| first_indexed | 2024-12-16T15:07:35Z |
| format | Article |
| id | doaj.art-59a2c0767a5640ff95dc20951a64dd3b |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-12-16T15:07:35Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-59a2c0767a5640ff95dc20951a64dd3b2022-12-21T22:27:04ZengElsevierEnvironment International0160-41202020-09-01142105833Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactationEiki Kimura0Go Suzuki1Naoto Uramaru2Toshihiro Endo3Fumihiko Maekawa4Center for Health and Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan; Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, JapanCenter for Material Cycles and Waste Management Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, JapanNihon Pharmaceutical University, 10281 Komuro Ina-machi, Kitaadachi-gun, Saitama 362-0806, JapanPhenovance Research & Technology, 5-4-19-302A, Kashiwanoha, Kashiwa, Chiba 277-0882, JapanCenter for Health and Environmental Risk Research, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan; Corresponding author.Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/DFs) have been unintentionally produced and emitted from the lifecycle of products containing brominated flame retardants, such as polybrominated diphenyl ether, which is suspected to cause developmental neurotoxicity (DNT). Although it is plausible that PBDD/DFs can also induce DNT, information regarding their neurotoxic potential is currently limited. Hence, in the present study, we examined the effects of in utero and lactational exposure to brominated dibenzofurans on infant and adult offspring behavior to understand the mechanism of PBDD/DFs toxicity and detect effective behavioral endpoints in DNT assessment. We analyzed the behavior of mouse offspring born to dams administered 2,3,7,8-tetrabromodibenzofuran (2,3,7,8-TeBDF; dose of 0, 9, or 45 μg/kg) or 2,3,8-tribromodibenzofuran (2,3,8-TrBDF; dose of 0, 75.6, or 378 μg/kg) on gestational day 12.5. In mouse offspring born to dams exposed to 2,3,7,8-TeBDF, the exploratory behavior in a novel environment in adulthood and ultrasonic vocalization (USV) during infancy were significantly reduced. Additionally, AhR-target genes, such as Cyp1a1, were induced in the liver of 2,3,7,8-TeBDF-exposed offspring in a dose-dependent manner. Conversely, no significant changes in the infant and adult behaviors and expression level of AhR-target genes were observed in the 2,3,8-TrBDF-exposed offspring. These results suggest that 2,3,7,8-TeBDF can induce DNT and that the analysis of exploratory behavior in a novel environment and USV may be useful endpoints to assess DNT of dioxin-related substances.http://www.sciencedirect.com/science/article/pii/S0160412020317888PBDD/DFsToxic equivalency factorDevelopmental neurotoxicityPerinatal exposureMouseBehavioral analysis |
| spellingShingle | Eiki Kimura Go Suzuki Naoto Uramaru Toshihiro Endo Fumihiko Maekawa Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation Environment International PBDD/DFs Toxic equivalency factor Developmental neurotoxicity Perinatal exposure Mouse Behavioral analysis |
| title | Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation |
| title_full | Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation |
| title_fullStr | Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation |
| title_full_unstemmed | Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation |
| title_short | Behavioral impairments in infant and adult mouse offspring exposed to 2,3,7,8-tetrabromodibenzofuran in utero and via lactation |
| title_sort | behavioral impairments in infant and adult mouse offspring exposed to 2 3 7 8 tetrabromodibenzofuran in utero and via lactation |
| topic | PBDD/DFs Toxic equivalency factor Developmental neurotoxicity Perinatal exposure Mouse Behavioral analysis |
| url | http://www.sciencedirect.com/science/article/pii/S0160412020317888 |
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