Thyroid disrupting effects of low-dose dibenzothiophene and cadmium in single or concurrent exposure: New evidence from a translational zebrafish model

Thyroid hormones (THs) are major regulators of biological processes essential for correct development and energy homeostasis. Although thyroid disruptors can deeply affect human health, the impact of exogenous chemicals and in particular mixture of chemicals on different aspects of thyroid development and metabolism is not yet fully understood. In this study we have used the highly versatile zebrafish model to assess the thyroid axis disrupting effects of cadmium (Cd) and dibenzothiophene (DBT), two environmental endocrine disruptors found to be significantly correlated in epidemiological co-exposure studies. Zebrafish embryos (5hpf) were exposed to low concentrations of Cd (from 0.05 to 2 ?M) and DBT (from 0.05 to 1 ?M) and to mixtures of them. A multilevel assessment of the pollutant effects has been obtained by combining in vivo morphological analyses allowed by the use of transgenic fluorescent lines with liquid chromatography mass spectrometry determination of TH levels and quantification of the expression levels of key genes involved in the Hypothalamic-Pituitary-Thyroid Axis (HPTA) and TH metabolism. Our results underscore for the first time an important synergistic toxic effect of these pollutants on embryonic development and thyroid morphology highlighting differences in the mechanisms through which they can adversely impact on multiple physiological processes of the HPTA and TH disposal influencing also heart geometry and function.