Effects of methimazole on the thyroid hormone system in Japanese medaka (Oryzias latipes) larvae

Thyroid hormones (THs) are essential for fish development, metabolism, and reproduction. Disruptions in TH balance caused by exposure to TH-disrupting chemicals (THDCs) can lead to serious physiological problems. While adverse outcome pathways (AOPs) for THDCs have been described in zebrafish and fathead minnows, similar pathways in Japanese medaka (Oryzias latipes) are still not well understood. In this study, we explored how methimazole (MMI), a thyroid peroxidase (TPO) inhibitor, affects the development of Japanese medaka, focusing on growth, swim bladder inflation, thyroid hormone (T4 and T3) levels, and gene expression patterns in this species. The results obtained indicated that MMI exposure suppressed T4 levels in a dose-dependent manner, but did not show any dose-dependent effects on the thyroid hormone-related genes expression levels or growth and the growth-related genes expression. Although the incidence of swim bladder inflation failure showed statistically significant differences, it was not dose-dependent; the inflation rate remained approximately 90 % across all exposure concentrations, suggesting no biologically meaningful effect. This observed disruption of T4 levels aligned with key events in established AOPs for THDCs. Furthermore, our findings provide valuable insights into the taxonomic domain of applicability for these AOPs.