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

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Toxicologic Pathology 2024, Vol.37(4), pp.173-187
Main Authors: Ogata, Keiko, Suto, Hidenori, Sato, Akira, Maeda, Keiko, Minami, Kenta, Tomiyama, Naruto, Kosaka, Tadashi, Hojo, Hitoshi, Takahashi, Naofumi, Aoyama, Hiroaki, Yamada, Tomoya
Format: Article
Language:English
Subjects:
comparative thyroid assay
developmental neurotoxicity
endocrine disruption
heterotopia
hypothyroidism
Original
thyroid hormone
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0914-9198
1881-915X
DOI:10.1293/tox.2024-0004