Abstract
The chemical-induced maternal hypothyroidism has been concerned to adversely affect the growth and brain development of offsprings. In 2018, therefore, the assessment of thyroid-related endpoints was added to related OECD test guidelines (TG). However, it is not fully understood the correlation between developmental toxicity and changes in maternal thyroid-related endpoints in pregnant mothers with mild hypothyroidism observed as chemical-induced thyroid dysfunction. In the present study, we conducted the prenatal developmental toxicity test according to the OECD TG414 and investigated the effects of various degree of maternal hypothyroidism on the fetal development in mice. Pregnant ICR mice were treated with propylthiouracil (PTU) containing food at the concentrations of 0, 2, 10, 50, 250 ppm from gestation day (GD) 6 to GD18, and dams and fetuses were analyzed at GD18. A significant decrease in the serum T3 and T4 levels and a significant increase in the serum TSH level were observed in 50 and 250 ppm PTU-treated dams. Moreover, histological abnormalities in the thyroid gland were observed in dams treated with more than 10 ppm of PTU. These results suggest that histological abnormalities in the thyroid are more sensitive biomarker to detecting hypothyroidism than changes in serum thyroid-related hormones. In addition, fetus exposed to maternal hypothyroidism did not show any developmental toxicity in the current experimental condition. Our findings will be useful in the development of management strategies for the safe use of chemicals that may induce hypothyroidism.
