Alterations in retinoid status after long-term exposure to PBDEs in zebrafish (Danio rerio)

This study examined the disruptive effect of exposure to polybrominated diphenyl ethers (PBDEs) on retinoid content in zebrafish (Danio rerio). Adult zebrafish were exposed to an environmentally relevant concentration (0.45 μg/L) and a higher concentration (9.6 μg/L) of DE-71 for 60 days. Retinoid content and gene transcription levels were examined in female zebrafish. PBDE exposure caused a significant decrease of retinyl ester content in the intestine and a downregulation of intestinal cellular retinol binding protein gene transcription (CRBP1a). In the liver, retinyl ester content was significantly decreased, while retinol content was increased. An upregulation of liver CRBP2a and retinol binding protein (RBP) gene transcription and an increased level of RBP protein were observed. In the eyes, both the retinal and retinyl ester content were increased and CRBP1a gene transcription was upregulated. However, the gene encoding for retinal dehydrogenase (RALDH2), responsible for retinoic acid synthesis, was downregulated in the eyes. CYP26a, the gene responsible for retinoic acid degradation, was upregulated, which indicated an increased level of retinoic acid. In the ovaries, the increased deposition of retinoids was also observed, while gene transcription levels of both CRBPs (CRBP1a and CRBP1b) were upregulated. An increased deposition of retinal was measured in the eggs. Overall, this study demonstrated that long-term exposure of zebrafish to environmentally relevant concentrations of DE-71 disrupted the transport, storage and metabolism of retinoid in various tissues. This study also indicated that retinoid levels in zebrafish are sensitive to PBDE exposure and highlighted the importance of liver storage, which appears to support important functions in reproduction and vision.

► Adult zebrafish were exposed to DE-71, and the retinoid concentrations and gene transcriptions linked to transport and metabolism of retinoids were examined in female zebrafish. DE-71 exposure disrupted retinoid transport, storage and metabolism in various tissue types.
► Increased retinol binding protein (RBP) levels were observed in liver and plasma samples. Increased deposition of retinoids was measured in ovaries, eyes and eggs.
► Retinoid levels in zebrafish are sensitive to PBDE exposure.
► The importance of retinoid liver storage to support important functions such as reproduction and vision was highlighted.