College of Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
College of Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
Aquat Toxicol. 2024 Oct;275:107063. doi: 10.1016/j.aquatox.2024.107063. Epub 2024 Aug 23.
Diazepam (DZP) is a universally detected emerging pollutant in aquatic ecosystems. Although the sex-dependent effects of DZP on fish have been properly established, the underlying mechanisms remain unclear. In this study, zebrafish of both sexes were separately exposed to DZP (8 μg/L) for 21 days, and the alteration of the behaviors, brain amino acid neurotransmitter contents, and transcriptomic profiles were investigated. Although DZP exposure showed a sedative effect on both sexes, significantly reduced cumulative duration of high mobility and willingness to encounter the opposite sex were only observed in females. However, DZP significantly enhanced the brain levels of glutamate and glutamine in males but not in females. Transcriptome analysis identified more different expression genes (DEGs) in females (322 up-regulated and 311 down-regulated) than in males (138 up-regulated genes and 38 down-regulated). The DEGs in both sexes were significantly enriched in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway of the synaptic vesicle cycle, indicating a possible pathway for the sedative effects of DZP on zebrafish. DZP exhibited different or even opposing regulatory patterns on gene expression in the brains of females and males, providing some insights into its sex-dependent impacts on the behaviors and brain neurotransmitter contents in zebrafish. Moreover, enrichment analysis also suggested that DZP exposure may affect the oocyte maturation in female zebrafish, which highlights the need to study its reproductive and transgenerational toxicity to fish species.
地西泮（DZP）是水生生态系统中普遍存在的新兴污染物。尽管 DZP 对鱼类的性别依赖性影响已得到充分证实，但潜在机制仍不清楚。在这项研究中，雌雄斑马鱼分别暴露于 DZP（8μg/L）中 21 天，研究了行为、大脑氨基酸神经递质含量和转录组谱的变化。尽管 DZP 暴露对雌雄鱼都有镇静作用，但仅在雌性鱼中观察到累积的高迁移性和与异性接触的意愿显著降低。然而，DZP 显著增加了雄性鱼而不是雌性鱼大脑中谷氨酸和谷氨酰胺的水平。转录组分析鉴定出雌性鱼中有更多不同表达的基因（DEGs）（322 个上调和 311 个下调），而雄性鱼中只有 138 个上调基因和 38 个下调基因。雌雄鱼的 DEGs 均显著富集在突触小泡循环的 KEGG（京都基因与基因组百科全书）途径中，表明 DZP 对斑马鱼的镇静作用可能存在一种途径。DZP 在雌性和雄性鱼的大脑基因表达上表现出不同的甚至相反的调控模式，为其对鱼类行为和大脑神经递质含量的性别依赖性影响提供了一些见解。此外，富集分析还表明，DZP 暴露可能会影响雌性斑马鱼的卵母细胞成熟，这突出了需要研究其对鱼类物种的生殖和跨代毒性。
