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• W3158414102 endingPage "112255" @default.
• W3158414102 startingPage "112255" @default.
• W3158414102 abstract "The aromatase inhibitor letrozole can be found in rivers, effluents, and even drinking water. Studies have demonstrated that letrozole affects various metabolic pathways and may cause reproductive toxicity, especially in fish exposed during development. However, studies on the effect of a low concentration of letrozole at the whole-gonad transcriptomic level in the early stage of fish sexual development have not been investigated. The aim of our study was to explore the potential effects of a low concentration of letrozole on the gonad transcriptome of Nile tilapia at an early stage of sexual development. In this study, 9 dpf (days postfertilization) Nile tilapia were exposed to trace letrozole for 12 days. Letrozole exposure from 9 dpf to 21 dpf persistently altered phenotypic sex development and induced the male-biased sex ratio. The transcriptome results showed that 1173 differentially expressed genes (DEGs) were present in the female control vs 1.5 μg/L letrozole-treated female comparison group and that 1576 DEGs were present in the 1.5 μg/L letrozole-treated female vs male control comparison group. Differentially expressed gene enrichment analysis revealed several crucial pathways, including the drug metabolism-cytochrome P450 pathway, the ErbB-PI3K/Akt/mTOR pathway, and the calcium signalling pathway. Further analysis of these identified DEGs indicated that some key genes correlated with metabolism and epigenetic regulation were significantly affected by letrozole, such as UDP-glucuronosyltransferase ( Ugt ), glutathione S-transferase omega-1 ( Gsto1 ), lysine-specific demethylase 6bb ( Kdm6bb , original name is Kdm6a ), jumonji and AT-rich interaction domain containing 2 ( Jarid2b , original name is Jarid2 ), growth arrest and DNA damage inducible gamma ( Gadd45g ), and chromobox protein 7 ( Cbx7 ). The qRT-PCR validation results for twelve DEGs showed that the Pearson’s correlation of the log 10 fold change values between the qPCR and RNA-Seq results was 0.90, indicating the accuracy and reliability of the RNA-Seq results. Our study is the first to report the effect of letrozole on the transcriptome of gonads from fish during early-stage sexual development. These findings will be useful for understanding the toxic effects and molecular mechanisms of letrozole exposure at the early stage of gonad development on the sexual development of aquatic organisms. • The transcriptome of undifferentiated gonads after letrozole exposure was studied. • Drug metabolism-cytochrome P450 pathway was identified using RNA-Seq. • Letrozole exposure activated E2 signalling and calcium signalling pathways. • Letrozole affected the transcription of genes related to epigenetic regulation." @default.
• W3158414102 created "2021-05-10" @default.
• W3158414102 creator A5009828453 @default.
• W3158414102 creator A5020785235 @default.
• W3158414102 creator A5044910780 @default.
• W3158414102 creator A5054244975 @default.
• W3158414102 creator A5060134414 @default.
• W3158414102 date "2021-07-01" @default.
• W3158414102 modified "2023-09-26" @default.
• W3158414102 title "Global expression response of genes in sex-undifferentiated Nile tilapia gonads after exposure to trace letrozole" @default.
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