Toxic effects and transcriptome analyses of zebrafish (Danio rerio) larvae exposed to benzophenones

Sunscreen chemicals, such as benzophenones (BPs), are common environmental contaminants that are posing a growing health concern due to their increasing presence in water, fish, and human systems. Benzoresorcinol (BP1), oxybenzone (BP3), and dioxybenzone (BP8) are the most commonly used BPs for their ability to protect from sunburn by absorbing a broad spectrum of ultraviolet radiation. In this study, zebrafish larvae were used as an in vivo model to investigate the potential risks and molecular mechanisms of the toxic effects of BPs. The effects of these BPs on the gene expression in the aryl hydrocarbon receptor pathway, estrogen receptor pathway, and sex differentiation were detected using quantitative real-time PCR. All BPs were found to function as agonists of the estrogen receptors α and β1, indicating that these BPs likely undergo similar molecular metabolism in vivo, whereby they can activate cytochrome P450 genes and promote the expression of CYP19A and DMRT1. Furthermore, the gene expression profile of larvae after BP3 exposure was evaluated using a whole transcriptome sequencing approach. BP3 affected estradiol biosynthesis and sex differentiation. It also regulated gonadotropin-releasing hormone, thus interfering with the endocrine system. As a xenobiotic toxicant, BP3 upregulated the expression of cytochrome P450 genes (CYP1A and CYP3A65) and glutathione metabolism-related genes (GSTA, GSTM, and GSTP). It also interfered with the nervous system by regulating the calcium signaling pathway. These findings will be useful for understanding the toxicity mechanisms and metabolism of BPs in aquatic organisms and promote the regulation of these chemicals in the environment.