Transcriptome Profiling of Etridiazole-Exposed Zebrafish (Danio rerio) Embryos Reveals Pathways Associated with Cardiac and Ocular Toxicities

Abstract

Etridiazole (EDZ) is a thiadiazole-containing fungicide commonly used to control Pythium and Phytophthora spp. Although previous studies have shown that EDZ is teratogenic, the exact molecular mechanisms underlying its toxicity remain unknown. In this study, a zebrafish (Danio rerio; ZF) model was used to explore the molecular pathways associated with EDZ toxicity. The whole transcriptome of ZF embryos exposed to 96 h of EDZ was analyzed, along with developmental abnormalities. EDZ-induced malformations were primarily related to the eyes, heart, and growth of the ZF. Compared to untreated ZF, etridiazole-treated ZF had 2882 differentially expressed genes (DEGs), consisting of 1651 downregulated genes and 1231 upregulated genes. Gene ontology enrichment analysis showed that DEGs were involved in biological processes, such as sensory perception, visual perception, sensory organ development, and visual system development, and showed transmembrane transporter and peptidase regulator activities. Metabolism, phototransduction, aminoacyl-tRNA biosynthesis, MAPK signaling pathway, calcium signaling pathway, and vascular smooth muscle contraction were among the most enriched KEGG pathways. The qPCR analyses of the eight random genes were in good agreement with the transcriptome data. These results suggest several putative mechanisms underlying EDZ-induced developmental deformities in ZF.

Comparing Ocular Toxicity of Legacy and Alternative Per- and Polyfluoroalkyl Substances in Zebrafish Larvae

“…The analyzed genes related to photoreceptors included cone-rod homeobox ( crx ), rhodopsin ( rho ), opsin 1 short-wave-sensitive 2 ( opsn1sw2 ), opsin 1 medium-wave-sensitive 1 ( opn1mw1 ), and opsin 1 long-wave-sensitive 1 ( opn1lw1 ) [ 24 ]. The analyzed genes related to phototransduction included recoverin 3 ( rcvrn3 ); cyclic nucleotide gated channel subunit alpha 1b ( cnga1b ); guanylate cyclase activator 1d ( guca1d ); guanylate cyclase activator 1e ( guca1e ); guanylate cyclase 2D, retinal ( gucy2d ); arrestin 3a, retinal (X-arrestin) ( arr3a ); arrestin 3b , retinal (X-arrestin) ( arr3b ); phosphodiesterase 6H, cGMP-specific, cone, gamma, paralog a ( pde6ha ); and G protein subunit alpha transducin 2 ( gnat2 ) [ 24 , 25 , 26 ].…”