Global expression response of genes in sex-undifferentiated Nile tilapia gonads after exposure to trace letrozole.
Global expression response of genes in sex-undifferentiated Nile tilapia gonads after exposure to trace letrozole.
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DOI：
10.1016/j.ecoenv.2021.112255
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发表时间：
2021-04
影响因子：
6.8
通讯作者：
Jian Teng;Yan Zhao;H. Chen;Liangyi Xue;X. Ji
中科院分区：
文献类型：
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作者：
Jian Teng;Yan Zhao;H. Chen;Liangyi Xue;X. Ji
芳香酶抑制剂来曲唑可以在河流，污水，甚至饮用水中找到。研究表明，来曲唑会影响多种代谢途径，并可能导致生殖毒性，尤其是在发育期间暴露于来曲唑的鱼类。然而，低浓度来曲唑在鱼类性发育早期全性腺转录组水平上的影响的研究还没有调查。本研究的目的是探讨低浓度来曲唑对尼罗罗非鱼性发育早期性腺转录组的潜在影响。在这项研究中，9 dpf（受精后天数）尼罗罗非鱼暴露于微量来曲唑12天。来曲唑从9 dpf到21 dpf的暴露持续改变了表型性别发育，并诱导了雄性偏向的性别比。转录组结果显示，在雌性对照组与1.5 μ g/L来曲唑给药雌性对照组中存在1173个差异表达基因（DEG），在1.5 μg/L来曲唑给药雌性对照组与雄性对照组中存在1576个DEG。差异表达基因富集分析揭示了几个关键途径，包括药物代谢-细胞色素P450途径、ErbB-PI 3 K/Akt/mTOR途径和钙信号传导途径。对这些DEGs的进一步分析表明，来曲唑对一些与代谢和表观遗传调控相关的关键基因，如UDP-葡萄糖醛酸转移酶（Ugt）、谷胱甘肽S-转移酶ω-1（Gsto 1）、赖氨酸特异性脱甲基酶6 bb（Kdm 6 bb，原名Kdm 6a），jumonji和AT丰富的相互作用域包含2（Jarid 2b，原名Jarid 2）、生长停滞和DNA损伤诱导γ（Gadd 45 g）和染色体盒蛋白7（Cbx 7）。12个DEG的qRT-PCR验证结果显示，qPCR和RNA-Seq结果之间的log 10倍变化值的Pearson相关性为0.90，表明RNA-Seq结果的准确性和可靠性。我们的研究是第一个报告来曲唑对鱼类性腺转录组在早期性发育的影响。这些发现将有助于了解来曲唑暴露于性腺发育早期对水生生物性发育的毒性效应及其分子机制。
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 isKdm6a), jumonji and AT-rich interaction domain containing 2 (Jarid2b, original name isJarid2), 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 log10fold changevalues 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.