South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in České Budějovice, Zátiší 728/II, 389 25 Vodňany, Czech Republic.
Laboratory of Gene Expression, Institute of Biotechnology-Biocev, Academy of Science of Czech Republic, 252 50 Vestec, Czech Republic.
Int J Mol Sci. 2022 Jun 7;23(12):6392. doi: 10.3390/ijms23126392.
DNA damage during early life stages may have a negative effect on embryo development, inducing mortality and malformations that have long-lasting effects during adult life. Therefore, in the current study, we analyzed the effect of DNA damage induced by genotoxicants (camptothecin (CPT) and olaparib) at different stages of embryo development. The survival, DNA fragmentation, transcriptome, and proteome of the endangered sturgeon were analyzed. Sturgeons are non-model fish species that can provide new insights into the DNA damage response and embryo development. The transcriptomic and proteomic patterns changed significantly after exposure to genotoxicants in a stage-dependent manner. The results of this study indicate a correlation between phenotype formation and changes in transcriptomic and proteomic profiles. CPT and olaparib downregulated oxidative phosphorylation and metabolic pathways, and upregulated pathways involved in nucleotide excision repair, base excision repair, and homologous recombination. We observed the upregulated expression of zona pellucida sperm-binding proteins in all treatment groups, as well as the upregulation of several glycolytic enzymes. The analysis of gene expression revealed several markers of DNA damage response and adaptive stress response, which could be applied in toxicological studies on fish embryos. This study is the first complex analysis of the DNA damage response in endangered sturgeons.
早期生命阶段的 DNA 损伤可能对胚胎发育产生负面影响，导致胚胎死亡和畸形，这些影响会在成年期持续存在。因此，在目前的研究中，我们分析了遗传毒性剂（喜树碱（CPT）和奥拉帕利）在胚胎发育的不同阶段诱导的 DNA 损伤的影响。分析了濒危鲟鱼的生存、DNA 碎片化、转录组和蛋白质组。鲟鱼是非模式鱼类物种，可以为 DNA 损伤反应和胚胎发育提供新的见解。暴露于遗传毒性剂后，转录组和蛋白质组的模式发生了显著变化，表现出明显的阶段依赖性。这项研究的结果表明表型形成与转录组和蛋白质组图谱的变化之间存在相关性。CPT 和奥拉帕利下调了氧化磷酸化和代谢途径，而上调了核苷酸切除修复、碱基切除修复和同源重组途径。我们观察到所有处理组中透明带精子结合蛋白的表达上调，以及几种糖酵解酶的上调。基因表达分析揭示了几种 DNA 损伤反应和适应性应激反应的标志物，这些标志物可应用于鱼类胚胎的毒理学研究。本研究是对濒危鲟鱼 DNA 损伤反应的首次综合分析。
