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DC Field | Value | Language |
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dc.contributor.author | Ramhøj, L | - |
dc.contributor.author | Guyot, R | - |
dc.contributor.author | Svingen, T | - |
dc.contributor.author | Kortenkamp, A | - |
dc.contributor.author | Flamant, F | - |
dc.contributor.author | Axelstad, M | - |
dc.date.accessioned | 2023-07-24T15:03:06Z | - |
dc.date.available | 2023-07-24T15:03:06Z | - |
dc.date.issued | 2023-07-07 | - |
dc.identifier | ORCID iDs: Louise Ramhøj https://orcid.org/0000-0002-0298-8003; Andreas Kortenkamp https://orcid.org/0000-0001-9055-9729. | - |
dc.identifier | 105445 | - |
dc.identifier.citation | Ramhøj, L. et al. (2023) ‘Is periventricular heterotopia a useful endpoint for developmental thyroid hormone system disruption in mouse toxicity studies?’, Regulatory Toxicology and Pharmacology,.142, 105445, pp. 1 - 5. doi: 10.1016/j.yrtph.2023.105445. | en_US |
dc.identifier.issn | 0273-2300 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/26847 | - |
dc.description | Data availability: Data will be made available on request. | - |
dc.description.abstract | In rats, hypothyroidism during fetal and neonatal development can disrupt neuronal migration and induce the formation of periventricular heterotopia in the brain. However, it remains uncertain if heterotopia also manifest in mice after developmental hypothyroidism and whether they could be used as a toxicological endpoint to detect TH-mediated effects caused by TH system disrupting chemicals. Here, we performed a mouse study where we induced severe hypothyroidism by exposing pregnant mice (n = 3) to a very high dose of propylthiouracil (PTU) (1500 ppm) in the diet. This, to obtain best chances of detecting heterotopia. We found what appears to be very small heterotopia in 4 out of the 8 PTU-exposed pups. Although the incidence rate could suggest some utility for this endpoint, the small size of the ectopic neuronal clusters at maximum hypothyroidism excludes the utility of heterotopia in mouse toxicity studies aimed to detect TH system disrupting chemicals. On the other hand, parvalbumin expression was manifestly lower in the cortex of hypothyroid mouse offspring demonstrating that offspring TH-deficiency caused an effect on the developing brain. Based on overall results, we conclude that heterotopia formation in mice is not a useful toxicological endpoint for examining TH-mediated developmental neurotoxicity. | en_US |
dc.description.sponsorship | EU Horizon 2020 programme to two projects: grant number 825161 for the project “ATHENA: Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies” (Kortenkamp et al., 2020), and grant number 825753 for the project “ERGO: Breaking Down the Wall Between Human Health and Environmental Testing of Endocrine Disruptors” (Holbech et al., 2020) as well as the Danish Environmental Protection Agency, Ministry of Environment of Denmark. | en_US |
dc.format.extent | 1 - 5 | - |
dc.format.medium | Print-Electronic | - |
dc.language | English | - |
dc.publisher | Elsevier | en_US |
dc.rights | Copyright © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | hypothyroidism | en_US |
dc.subject | endocrine disruption | en_US |
dc.subject | thyroid disruption | en_US |
dc.subject | thyroid hormone | en_US |
dc.subject | thyroid | en_US |
dc.subject | HPT-Axis | en_US |
dc.subject | developmental neurotoxicity | en_US |
dc.subject | brain | en_US |
dc.subject | migration | en_US |
dc.subject | parvalbumin | en_US |
dc.title | Is periventricular heterotopia a useful endpoint for developmental thyroid hormone system disruption in mouse toxicity studies? | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1016/j.yrtph.2023.105445 | - |
dc.relation.isPartOf | Regulatory Toxicology and Pharmacology | - |
pubs.publication-status | Published | - |
pubs.volume | 142 | - |
dc.identifier.eissn | 1096-0295 | - |
dc.rights.holder | The Authors | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) | 3.55 MB | Adobe PDF | View/Open |
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