Mechanism of thyroid hormone and its structurally similar contaminant bisphenol S exposure on retinoid metabolism in zebrafish larval eyes.

[Display omitted] • BPS stimulated atRA metabolism mainly to 18-OH metabolite in zebrafish eyes, like T3. • CYP26A1 is necessary for atRA metabolism and retinoids regeneration in visual cycle. • TRβ mediated cyp26a1 expression, and BPS and T3 stimulated the expression of cyp26a1 via TRβ. • BPS disturbed CYP26A1-mediated visual retinoids metabolism via TRβ in zebrafish eyes. The photoreceptor necessitates the retinoids metabolism processes in visual cycle pathway to regenerate visual pigments and sustain vision. Bisphenol S (BPS), with similar structure of thyroid hormone (TH), was reported to impair the light-sensing function of zebrafish larvae via disturbing TH-thyroid hormone receptor β (TR β) signaling pathway. However, it remains unknown whether TR β could modulate the toxicity of BPS on retinoid metabolism in visual cycle. This study showed that BPS diminished the optokinetic response of zebrafish larvae and had a stimulative effect on all- trans -retinoic acid (atRA) metabolism, like exogenous T3 exposure. By modulating CYP26A1 and TR β expression, it was found that CYP26A1 played a crucial role in catalyzing oxidative metabolism of atRA and retinoids regeneration in visual cycle, and TR β mediated cyp26a1 expression in zebrafish eyes. Similar with 10 nM T3 treatment, cyp26a1 expression could be induced by BPS in the presence of TR β. Further, in CYP26A1 and TR β - deficient eyes, 100 μg/L BPS could no longer promote atRA metabolism, or decrease the all- trans -retinol and 11-cis retinal contents in visual cycle, demonstrating that BPS exposure disturbed CYP26A1-mediated visual retinoids metabolism via TR β. Overall, this study highlights the role of TR β in mediating the retinoids homeostasis disruption caused by BPS, and provides new clues for exploring molecular targets of visual toxicity under pollutants stress. [ABSTRACT FROM AUTHOR]