miR-424/322 is downregulated in the semen of patients with severe DNA damage and may regulate sperm DNA damage.
miR-424/322 is downregulated in the semen of patients with severe DNA damage and may regulate sperm DNA damage.
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DOI：
10.1071/rd15052
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
K. Zhao;Yaoping Chen;Rui Yang;Yang Bai;Cuiling Li;Honggang Li;Chengliang Xiong
中科院分区：
文献类型：
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作者：
K. Zhao;Yaoping Chen;Rui Yang;Yang Bai;Cuiling Li;Honggang Li;Chengliang Xiong
精子DNA的完整性是准确传递遗传信息的重要因素。人类精子DNA损伤是男性不育的常见原因，但确切的机制仍不清楚。考虑到microRNA(MiRNA)在多种病理生理过程中的重要作用，我们假设睾丸miRNA参与了精子发生过程中精子DNA的损伤。从1090例男性不育患者中筛选出94例精子DNA片段指数(DFI)较高的不育症患者，并从精浆中筛选出18个睾丸特异的miRNAs进行检测。MIR-29c和miR-424在高DFI男性中表达下调。这两个miRNAs在小鼠体内的抑制证实了miR-424(小鼠同源miR-322)在精子发生过程中对精子DNA损伤的作用；相比之下，miR-29c的结果为阴性。因此，miR-424/322参与了精子DNA损伤。此外，该miRNA的失调可在精子发生过程中诱导DNA双链断裂。
Sperm DNA integrity is an essential factor for accurate transmission of genetic information. Human sperm DNA damage is a common cause of male infertility but the exact mechanism remains poorly understood. Considering the vital role of microRNA (miRNA) in multiple pathophysiological processes, we hypothesised that testicular miRNA is involved in sperm DNA damage during spermatogenesis. Infertile patients with high sperm DNA fragment index (DFI; n=94) were selected from 1090 infertile men and a total of 18 testis-specific seminal miRNAs previously identified from human seminal plasma were chosen and tested. miR-29c and miR-424 were downregulated in men with high DFI. The inhibition of these two miRNAs in mice confirmed the role of miR-424 (murine homologue miR-322) in sperm DNA damage during spermatogenesis; by contrast, miR-29c exhibited a negative result. Thus, miR-424/322 is involved in sperm DNA damage. Furthermore, the dysregulation of this miRNA can induce DNA double-strand breaks during spermatogenesis.