MTHFR promoter hypermethylation in testicular biopsies of patients with non-obstructive azoospermia: the role of epigenetics in male infertility
MTHFR promoter hypermethylation in testicular biopsies of patients with non-obstructive azoospermia: the role of epigenetics in male infertility
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DOI：
10.1093/humrep/dep194
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发表时间：
2009-09-01
影响因子：
6.1
通讯作者：
Pujol, P.
中科院分区：
文献类型：
--
作者：
Khazamipour, N.;Noruzinia, M.;Pujol, P.
男性不育症的病因机制仍然知之甚少。亚甲基四氢叶酸还原酶（MTHFR）基因突变已被证明与男性不育有关;然而，其他发病机制，如启动子超甲基化，也可能发挥作用。因此，本研究比较了非梗阻性无精子症（NOA）和无精子发生异常的梗阻性无精子症患者MTHFR基因启动子区的甲基化状态。（对照）以及来自32名NOA患者和5名梗阻性无精子血症患者的睾丸活检的DNA，但精子发生正常，甲基化特异性聚合酶链反应（Methylation Specific PCR，PCR）检测外周血淋巴细胞MTHFR基因启动子区的甲基化水平，结果显示，外周血淋巴细胞MTHFR基因启动子区的甲基化水平与正常对照组无明显差异。NOA患者睾丸组织中甲基化率为53%，而梗阻性无精子症患者睾丸组织中甲基化率为0%（P = 0.03），表明NOA患者睾丸组织中甲基化是特异性的，而不是由于普遍的甲基化缺陷所致，提示MTHFR的表观遗传沉默可能在无精子症不育中发挥作用。
The causative mechanisms of male infertility are still poorly understood. Mutations in the Methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be involved in male infertility; however, other mechanisms of pathogenesis, like promoter hyper-methylation, could also play a role. Therefore, in this study we compared the methylation status of the promoter region of MTHFR in male patients with non-obstructive azoospermia (NOA) and obstructive azoospermia without anomalies of spermatogenesis.DNA from peripheral blood (PB) samples of 50 patients with NOA and 50 fertile men (controls) as well as DNA from testicular biopsies of 32 patients with NOA and five patients with obstructive azoospemia, but normal spermatogenesis, were analyzed by Methylation Specific PCR amplification using primers that hybridize to the CpG island in the promoter region of MTHFR.In PB, no differences in the methylation profile of the promoter region of MTHFR were observed between patients and controls. In testis biopsies, hyper-methylation was detected in 53% of the patients with NOA compared with 0% of patients with obstructive azoospermia (P = 0.03).These results indicate that hyper-methylation in testis DNA from NOA patients is specific and not due a general methylation defect, and suggest that epigenetic silencing of MTHFR could play a role in azoospermic infertility.