Analysis of Differential Gene Expression under Acute Lead or Mercury Exposure in Larval Zebrafish Using RNA-Seq

This study was first conducted to investigate the effects of acute lead exposure on developing zebrafish embryos or larvae from 24 to 120 h post-fertilization (hpf). Our data showed that treatment with 50-200 μM lead significantly affected larval survivability and morphology compared to the respective control. Second, we chose 120 hpf larvae treated with 12.5 μM lead for RNA sequencing due to its exposure level being sufficient to produce toxic effects with minimum death and lead bioaccumulation in developing zebrafish. A total of 137.45 million raw reads were obtained, and more than 86% of clean data were mapped to the zebrafish reference genome. Differential expression profiles generated 116 up- and 34 down-regulated genes upon lead exposure. The most enriched GO terms for representative DEGs were ion transport and lipid metabolism. Third, a comparison with the dataset of mercury-regulated gene expression identified 94 genes (64 up-regulated and 30 down-regulated) for exposure specific to lead, as well as 422 genes (338 up-regulated and 84 down-regulated) for exposure specific to mercury. In addition, 56 genes were co-regulated by micromolar mercury and lead treatment, and the expression of thirteen genes, including <i>mt2</i>, <i>ctssb.1</i>, <i>prdx1</i>, <i>txn</i>, <i>sqrdl</i>, <i>tmprss13a</i>, <i>socs3a</i>, <i>trpv6</i>, <i>abcb6a</i>, <i>gsr</i>, <i>hbz</i>, <i>fads2,</i> and <i>zgc:92590</i> were validated by qRT-PCR. These genes were mainly associated with metal ion binding, proteolysis, antioxidant activity, signal transduction, calcium ion or oxygen transport, the fatty acid biosynthetic process, and protein metabolism. Taken together, these findings help better understand the genome-wide responses of developing zebrafish to lead or mercury and provide potential biomarkers for acute exposure to toxic metals.