The Affiliated Hospital of Medical School, Ningbo University, Ningbo 315020, China.
School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China; State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Sci Total Environ. 2022 Nov 25;849:157726. doi: 10.1016/j.scitotenv.2022.157726. Epub 2022 Jul 29.
Antibiotic residues in the aquatic environment have been shown to induce significant adverse effects on the early-life stage development of aquatic organisms, though the underlying molecular mechanisms of these effects have not been well characterized. In this study, we performed global mRNA-miRNA sequencing, canonical pathway analyses, morphological, physiological, immunohistochemical, and behavioral analyses to comprehensively assess the cross-generational cardiotoxicity and mechanisms of antibiotic mixtures in zebrafish. Following parental treatment to 1 and 100 μg/L antibiotic mixtures (15 of the most commonly detected antibiotics) for 150 days, all 15 assessed antibiotics were detected in the F1 eggs, indicating the cross-generational transfer of antibiotics. Global mRNA-miRNA sequencing functional analysis predicted cardiotoxicity in the F1 generation by using the F1 whole fish. Consistent with canonical pathway analyses, significant cardiotoxicity was observed in F1 larvae, as well as the apoptosis of cardiac cells. Furthermore, let-7a-5p regulated the cardiac hypertrophy signaling pathway, suggesting mechanisms of miRNA of let-7 family mediating cross-generational cardiotoxicity of antibiotics in zebrafish. This study lays some groundwork for developing interventions to prevent parental exposure to environmental pollutants such as antibiotics from adversely affecting offspring development.
水环境中的抗生素残留已被证明会对水生生物的早期发育阶段产生重大的不利影响，尽管这些影响的潜在分子机制尚未得到很好的描述。在这项研究中，我们进行了全局 mRNA-miRNA 测序、经典途径分析、形态学、生理学、免疫组织化学和行为分析，以全面评估抗生素混合物在斑马鱼中的跨代心脏毒性及其机制。在对亲鱼进行 150 天 1 和 100 μg/L 抗生素混合物（最常检测到的 15 种抗生素）处理后，所有 15 种评估的抗生素都在 F1 卵中被检测到，表明抗生素的跨代转移。全局 mRNA-miRNA 测序功能分析使用 F1 整条鱼预测了 F1 代的心脏毒性。与经典途径分析一致，在 F1 幼虫以及心脏细胞凋亡中观察到明显的心脏毒性。此外，let-7a-5p 调控心脏肥大信号通路，表明 let-7 家族的 miRNA 介导抗生素在斑马鱼中的跨代心脏毒性的机制。这项研究为制定干预措施奠定了基础，以防止亲鱼暴露于环境污染物（如抗生素），从而避免对后代发育产生不利影响。
