Preself-Feeding Medaka Fry Provides a Suitable Screening Systemforin VivoAssessment of Thyroid Hormone-Disrupting Potential

Endocrine-disrupting chemicals are assessed based on theirphysiological potential and their potential associated adverse effects. However,suitable end points for detection of chemicals that interfere with the thyroidhormone (TH) system have not been established in nonmammals, with theexception of amphibian metamorphosis. The aims of the current study were todevelop anin vivoscreening system using preself-feeding medaka fry (Oryziaslatipes) for the detection of TH-disrupting chemicals and elucidate theunderlying molecular mechanism. 17 alpha-Ethinylestradiol (EE2: <100 ng/L) didnot induce mRNA expression of estrogen-responsive genes,vitellogenins(vtgs)mRNA. Meanwhile, coexposure with thyroxin (T4) induced an increase ofvtgexpression. TH-disrupting chemicals (thiourea (TU), perfluorooctanoic acid(PFOA), and tetrabromobisphenol A (TBBPA)) significantly suppressed EE2(1,000 ng/L)-inducedvtg1expression, while T4 rescued their expression aswell as that ofthyroid hormone receptor alpha(tR alpha) andestrogen receptors(esrs). These results were supported byin silicoanalysis of the5 '-transcriptional regulatory region of these genes. Furthermore, theesr1null mutant revealed that EE2-inducedvtg1expressionrequires mainlyesr2aandesr2bin a TH-dependent manner in preself-feeding fry. Application of preself-feeding medaka fry as ascreening system might help decipher thein vivomechanisms of action of TH-disrupting molecules, while providing an alternative tothe traditional animal model.