Developmental toxicity and transcriptome analysis of 4-epianhydrotetracycline to zebrafish (Danio rerio) embryos

As a primary degradation by-product of tetracycline (TC), 4-Epianhydrotetracycline (4-EATC) has been detected frequently in the aquatic environment, which may pose a potential environmental risk to aquatic organisms. Up to now, however, the toxicology study on 4-EATC to aquatic organisms is limited. In the present study, in order to better understand the toxic mechanism of 4-EATC, developmental toxicity including lethal and sublethal effects of 4-EATC and TC were investigated. The results showed that the developmental toxicity of 4-EATC to zebrafish embryos was stronger than that of TC. The 96 h LC50 value of 4-EATC to zebrafish embryos was 29.13 mg/L. Malformations seemed to be the most sensitive sublethal endpoint of 4-EATC exposure, and the 96 h EC50 value was 8.57 mg/L. Transcriptome response of 4-EATC to zebrafish embryos was determined. The results showed that 430 different expression genes (DEGs) caused by 4-EATC, and most enriched in tryptophan (TRP) metabolism pathway. Annotation of DEGs in the TRP metabolism demonstrated that expression of 4 gene products in tryptophan metabolized along the kynurenine (KYN) pathway were changed. Disorder of TRP catabolism in KYN pathway was a potential mechanism of 4-EATC toxicity to zebrafish embryos.