Departments of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China; Departments of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China.
Departments of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310053, PR China.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):838-845. doi: 10.1016/j.bbrc.2018.04.200. Epub 2018 May 19.
Glyphosate is the active ingredient in numerous herbicide formulations. The roles of glyphosate in embryo-toxicity and neurotoxicity have been reported in human and animal models. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. However, the role of glyphosate in neuronal development is still not fully understood. Our previous study found that perinatal glyphosate exposure resulted in differential microRNA expression in the prefrontal cortex of mouse offspring. However, the mechanism of glyphosate-induced neurotoxicity in the developing brain is still not fully understood. Considering the pivotal role of Circular RNAs (circRNAs) in the regulation of gene expression, a circRNA microarray method was used in this study to investigate circRNA expression changes in the hippocampus of mice with perinatal glyphosate exposure. The circRNA microarrays revealed that 663 circRNAs were significantly altered in the perinatal glyphosate exposure group compared with the control group. Among them, 330 were significantly upregulated, and the other 333 were downregulated. Furthermore, the relative expression levels of mmu-circRNA-014015, mmu-circRNA-28128 and mmu-circRNA-29837 were verified using quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that stress-associated steroid metabolism pathways, such as aldosterone synthesis and secretion pathways, may be involved in the neurotoxicity of glyphosate. These results showed that circRNAs are aberrantly expressed in the hippocampus of mice with perinatal glyphosate exposure and play potential roles in glyphosate-induced neurotoxicity.
草甘膦是多种除草剂配方中的有效成分。在人类和动物模型中已经报道了草甘膦在胚胎毒性和神经毒性中的作用。最近,几项研究报告了有证据表明神经发育障碍(NDD)与妊娠期草甘膦暴露有关。然而,草甘膦在神经元发育中的作用仍不完全清楚。我们之前的研究发现,围产期草甘膦暴露导致了小鼠后代前额叶皮质中差异表达的 microRNA。然而,草甘膦诱导的发育期大脑神经毒性的机制仍不完全清楚。考虑到环状 RNA(circRNA)在基因表达调控中的关键作用,本研究采用 circRNA 微阵列方法研究了围产期草甘膦暴露小鼠海马中 circRNA 的表达变化。circRNA 微阵列显示,与对照组相比,围产期草甘膦暴露组有 663 个 circRNA 显著改变。其中,330 个明显上调,另外 333 个下调。此外,采用定量实时聚合酶链反应(qRT-PCR)验证了 mmu-circRNA-014015、mmu-circRNA-28128 和 mmu-circRNA-29837 的相对表达水平。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,应激相关的类固醇代谢途径,如醛固酮合成和分泌途径,可能与草甘膦的神经毒性有关。这些结果表明,circRNA 在围产期草甘膦暴露的小鼠海马中异常表达,并在草甘膦诱导的神经毒性中发挥潜在作用。