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

Abstract

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 (TRβ) signaling pathway. However, it remains unknown whether TRβ 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 TRβ expression, it was found that CYP26A1 played a crucial role in catalyzing oxidative metabolism of atRA and retinoids regeneration in visual cycle, and TRβ mediated cyp26a1 expression in zebrafish eyes. Similar with 10 nM T3 treatment, cyp26a1 expression could be induced by BPS in the presence of TRβ. Further, in CYP26A1 and TRβ- 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 TRβ. Overall, this study highlights the role of TRβ in mediating the retinoids homeostasis disruption caused by BPS, and provides new clues for exploring molecular targets of visual toxicity under pollutants stress.

Keywords

• Bisphenol S
• Thyroid hormone
• Thyroid hormone receptor β
• CYP26A1
• Retinoids metabolism