Waterborne exposure of zebrafish embryos to micromole concentrations of ioxynil and diethylstilbestrol disrupts thyrocyte development

The herbicide ioxynil (IOX) and synthetic estrogen diethylstilbestrol (DES) are common aquatic contaminants with an endocrine disrupting action. In juvenile teleost fish IOX and DES disrupt the hypothalamic-pituitary-thyroid (HPT) axis. To assess how IOX and DES influence the developing HPT axis prior to establishment of central regulation of thyroid hormones, zebrafish embryos were exposed to low concentrations of the chemicals in water. IOX and DES (1 and 0.1μM) exposure failed to modify hypothalamic development but had a negative effect on thyrocyte development. Specifically, IOX and DES caused a significant (p<0.05) reduction in the size of the thyroid anlagen by decreasing the mRNA expression field of both nk2.1a and thyroglobulin (Tg) genes. Inhibition of thyroid gland development by IOX and DES (0.1μM) was strongly associated with altered heart morphology. To test if the effect of IOX and DES on the thyroid was a consequence of altered cardiac development a morpholino (MO) against zebrafish cardiac troponin I (zcTnI) was microinjected. The zcTnI morphants had modified heart function, a small thyroid anlagen and a reduction in the mRNA expression of nk2.1a and Tg genes similar to that of zebrafish exposed to IOX (1 and 0.1μM) and DES (0.1μM). Collectively the data indicate that IOX and DES alter thyroid development in zebrafish and chemicals that alter heart development and function can have an indirect endocrine disrupting action on the thyroid in teleosts.