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Upregulated microRNA‐423‐5p promotes oxidative stress through targeting glutathione S‐transferase mu 1 in asthenozoospermia
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2021-01-28 , DOI: 10.1002/mrd.23454
Rongxue Zhang 1 , Yanghua Zuo 1 , Senyang Cao 1
Affiliation  

The dysregulation of microRNAs (miRNAs) plays an important role in asthenozoospermia. This study evaluated the sperm microRNA‐423‐5p (miR‐423‐5p) expression in asthenozoospermia and normozoospermia, exploring the role of miR‐423‐5p in asthenozoospermia. Eighty participants were divided into asthenozoospermic (AZS, n = 40) and normozoospermic (Norm, n = 40) groups. Fresh semen samples were collected and the sperm cells were separated. Quantitative Real‐Time polymerase chain reaction was used to measure the sperm miR‐423‐5p level. Receiver operating characteristic curve (ROC) was employed to test the diagnostic performance of miR‐423‐5p in asthenospermia. Dual‐reporter luciferase assay was adopted to confirm the target gene of miR‐423‐5p. The target gene level in asthenozoospermia and normozoospermia was measured, and the biological function of target gene in asthenozoospermia was evaluated. Results showed that the miR‐423‐5p expression level in the AZS group was higher than that in Norm group, which was positively correlated with the severity of asthenozoospermia. ROC analysis of miR‐423‐5p showed an area under curve (AUC) of 0.69 (95% confidence interval = 0.57–0.80, p <0 .01), with 80% sensitivity and 60% specificity. Glutathione S‐transferase mu 1 (GSTM1) is a target gene of miR‐423‐5p, which significantly decreased in the AZS group. Compared with Norm group, glutathione S‐transferase (GST) activity and total antioxidant capacity (TAC) level decreased, while malondialdehyde (MDA) level increased in the AZS group. Furthermore, GST activity and TAC level were negatively correlated with miR‐423‐5p expression, while MDA level was positively correlated with miR‐423‐5p expression. In conclusion, the sperm miR‐423‐5p level significantly was upregulated in asthenozoospermia. High‐level miR‐423‐5p inhibited sperm motility through targeting GSTM1 to promote oxidative stress.

中文翻译:

上调的 microRNA-423-5p 通过靶向谷胱甘肽 S-转移酶 mu 1 在弱精子症中促进氧化应激

microRNA (miRNA) 的失调在弱精子症中起重要作用。本研究评估了精子 microRNA-423-5p (miR-423-5p) 在弱精子症和正常精子症中的表达,探索了 miR-423-5p 在弱精子症中的作用。80 名参与者被分为弱精子症 (AZS, n  = 40) 和正常精子症(Norm, n = 40) 组。收集新鲜精液样本并分离精细胞。定量实时聚合酶链反应用于测量精子 miR-423-5p 水平。接受者操作特征曲线(ROC)用于测试 miR-423-5p 在弱精子症中的诊断性能。采用双报告荧光素酶测定法确认miR-423-5p的靶基因。测定弱精子症和正常精子症的靶基因水平,评价靶基因在弱精子症中的生物学功能。结果显示,AZS组miR-423-5p表达水平高于Norm组,与弱精子症严重程度呈正相关。miR-423-5p 的 ROC 分析显示曲线下面积 (AUC) 为 0.69(95% 置信区间 = 0.57-0.80,p  <0 .01),灵敏度为 80%,特异性为 60%。谷胱甘肽 S-转移酶 mu 1 ( GSTM1 ) 是 miR-423-5p 的靶基因,在 AZS 组中显着降低。与Norm组相比,AZS组谷胱甘肽S-转移酶(GST)活性和总抗氧化能力(TAC)水平降低,而丙二醛(MDA)水平升高。此外,GST活性和TAC水平与miR-423-5p表达呈负相关,而MDA水平与miR-423-5p表达呈正相关。总之,精子 miR-423-5p 水平在弱精子症中显着上调。高水平 miR-423-5p 通过靶向GSTM1促进氧化应激抑制精子活力。
更新日期:2021-03-01
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