Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.

Autor:	Ogata K; Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka 554-8558, Japan., Suto H; Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka 554-8558, Japan.; Current address: Registration & Regulatory Affairs Department, AgroSolutions Division-International, Sumitomo Chemical Company, Ltd., Tokyo Nihombashi Tower, 2-7-1 Nihonbashi, Chuo-ku, Tokyo 103-6020, Japan., Sato A; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Maeda K; Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka 554-8558, Japan., Minami K; Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka 554-8558, Japan., Tomiyama N; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Kosaka T; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Hojo H; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Takahashi N; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Aoyama H; Institute of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043, Japan., Yamada T; Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 3-1-98 Kasugade-naka 3-chome, Konohana-ku, Osaka 554-8558, Japan.
Jazyk:	angličtina
Zdroj:	Journal of toxicologic pathology [J Toxicol Pathol] 2024 Oct; Vol. 37 (4), pp. 173-187. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1293/tox.2024-0004
Abstrakt:	In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3-6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design. Competing Interests: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study. (©2024 The Japanese Society of Toxicologic Pathology.)
Databáze:	MEDLINE
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