A Novel Transgenic Model to Study Thyroid Axis Activity in Early Life Stage Medaka

Identifying endocrine
disrupting chemicals in order to limit their
usage is a priority and required according to the European Regulation.
There are no Organization for Economic Co-operation and Development
(OECD) test guidelines based on fish available for the detection of
Thyroid axis Active Chemicals (TACs). This study aimed to fill this
gap by developing an assay at eleuthero-embryonic life stages in a
novel medaka (Oryzias latipes) transgenic line. This
transgenic line expresses green fluorescent protein (GFP) in thyrocytes,
under the control of the medaka thyroglobulin gene
promoter. The fluorescence expressed in the thyrocytes is inversely
proportional to the thyroid axis activity. When exposed for 72 h to
activators (triiodothyronine (T3) and thyroxine (T4)) or inhibitors (6-N-propylthiouracil (PTU),
Tetrabromobisphenol A (TBBPA)) of the thyroid axis, the thyrocytes
can change their size and express lower or higher levels of fluorescence,
respectively. This reflects the regulation of thyroglobulin by the
negative feedback loop of the Hypothalamic–Pituitary–Thyroid
axis. T3, T4, PTU, and TBBPA induced fluorescence
changes with the lowest observable effect concentrations (LOECs) of
5 μg/L, 1 μg/L, 8 mg/L, and 5 mg/L, respectively. This
promising tool could be used as a rapid screening assay and also to
help decipher the mechanisms by which TACs can disrupt the thyroid
axis in medaka.