Studying the mechanism of sperm DNA damage caused by folate deficiency.
Studying the mechanism of sperm DNA damage caused by folate deficiency.
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DOI：
10.1111/jcmm.17119
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发表时间：
2022-03
影响因子：
5.3
通讯作者：
Zhao K
中科院分区：
文献类型：
--
作者：
Wang W;Peng M;Yuan H;Liu C;Zhang Y;Fang Y;Su Y;Zhang X;Zhang H;Tang Y;Zhao K
精子DNA损伤是男性不育的常见原因之一。叶酸缺乏会增加重要基因的甲基化水平，包括那些参与 DNA 双链断裂 (DSB) 修复途径的基因。前期，我们分析了157名不孕症患者和91名捐精志愿者的精浆叶酸浓度与精液参数的相关性，发现精浆叶酸浓度与精子DNA碎片指数（DFI；r=-0.495，p<0.01）存在显着负相关。然后通过还原代表性亚硫酸氢盐测序，对低叶酸组和高叶酸组患者精子的整体DNA甲基化进行分析，发现叶酸缺乏组与正常叶酸组相比，Rad54启动子区甲基化水平升高。同时，动物模型和精母细胞系（GC-2）的结果也发现，叶酸缺乏可以增加Rad54启动子区甲基化水平，增加小鼠精子DFI，增加γ-H2AX（即DNA损伤标志蛋白）的表达，增加GC-2对外界损伤和刺激的敏感性。研究表明，叶酸缺乏会通过 DNA 甲基化下调 Rad54 的表达。 这可能是叶酸缺乏引起精子DNA损伤的机制之一。
Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double‐strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = −0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC‐2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ‐H2AX, that is, DNA injury marker protein, and increased sensitivity of GC‐2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.
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