Host: The Japanese Society of Toxicology
Name : The 52nd Annual Meeting of the Japanese Society of Toxicology
Date : July 02, 2025 - July 04, 2025
Maternal hypothyroidism during pregnancy has been linked to impaired brain development in offspring, raising concerns about the effects of thyroid-disrupting chemicals on child health. In response, thyroid-related parameters have been included in toxicological guideline studies since around 2016. However, the relationship between these parameters and developmental outcomes in offspring remains unclear, and an effective risk assessment framework is still lacking. While phenotypes of congenital hypothyroidism show that thyroid hormone deficiency during pregnancy and the perinatal period can affect offspring development, chemically induced hypothyroidism is generally mild and may not result in phenotypes seen in typical hypothyroid conditions. Therefore, identifying the most sensitive developmental endpoints in offspring affected by mild maternal thyroid hormone disruption is critical for chemical risk assessment. This issue was also highlighted at the 2019 Thyroid Hormone Assessment Workshop, hosted by HESI in the United States. To address this, we developed a mouse model of hypothyroidism using a thyroid peroxidase inhibitor propylthiouracil and examined sensitive developmental endpoints in the offspring. We found that the brain was the most sensitive target. Notably, these effects were not detected by conventional histopathology used in guideline studies, but were revealed using our original reporter mouse expressing luciferase under the control of a neural differentiation marker promoter.In this talk, I will present correlations between thyroid-related indicators and offspring developmental endpoints using this model and discuss challenges and perspectives in risk assessment of thyroid-disrupting chemicals.
