Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality.
Genome-wide 5-hydroxymethylcytosine patterns in human spermatogenesis are associated with semen quality.
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DOI：
10.18632/oncotarget.18331
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发表时间：
2017-10-24
期刊：
影响因子：
--
通讯作者：
Baranov VS
中科院分区：
文献类型：
--
作者：
Efimova OA;Pendina AA;Tikhonov AV;Parfenyev SE;Mekina ID;Komarova EM;Mazilina MA;Daev EV;Chiryaeva OG;Galembo IA;Krapivin MI;Glotov OS;Stepanova IS;Shlykova SA;Kogan IY;Gzgzyan AM;Kuznetzova TV;Baranov VS
我们对来自无精子患者的人睾丸生精细胞、来自捐精者的射精细胞和来自不育夫妇的患者的精子进行了DNA羟甲基化和甲基化的免疫荧光分析。与整个精子发生过程中存在的甲基化相反，在生精细胞和射精精子中，羟甲基化要么很高，要么几乎检测不到。在睾丸细胞遗传学制剂中，5-羟甲基胞嘧啶在有丝分裂和减数分裂染色体中检测不到，并且仅存在于期间精原细胞Ad和少量精细胞群体中。样品中羟甲基化和非羟甲基化二倍体和单倍体细胞核的比例相似，表明在分化的生精细胞中观察到的5-羟甲基胞嘧啶模式的改变是程序化的。在射精中，少数精子具有高的5-羟甲基胞嘧啶水平，而在其他精子中几乎检测不到羟甲基化。高度羟甲基化（5-羟甲基胞嘧啶阳性）精子的百分比在个体之间差异很大。在不育夫妇中，这一比例高于捐精者（P<0.0001），且差异范围更大：0.12-21.24%比0.02-0.46%。高度羟甲基化精子的百分比与精液质量良好的指标——正常形态（r=-0.567， P<0.0001）和头部形态正常（r=-0.609， P<0.0001）呈强烈负相关，与精液质量差的指标——精子DNA碎片化呈强烈正相关（r=0.46， P=0.001）。因此，免疫细胞化学检测到单个精子中5hmC的增加与夫妇不育和精子参数的恶化有关。我们假设这种增加不是程序化的，而是一种诱导异常，因此，它可能被用作精液质量的新指标。
We performed immunofluorescent analysis of DNA hydroxymethylation and methylation in human testicular spermatogenic cells from azoospermic patients and ejaculated spermatozoa from sperm donors and patients from infertile couples. In contrast to methylation which was present throughout spermatogenesis, hydroxymethylation was either high or almost undetectable in both spermatogenic cells and ejaculated spermatozoa. On testicular cytogenetic preparations, 5-hydroxymethylcytosine was undetectable in mitotic and meiotic chromosomes, and was present exclusively in interphase spermatogonia Ad and in a minor spermatid population. The proportions of hydroxymethylated and non-hydroxymethylated diploid and haploid nuclei were similar among samples, suggesting that the observed alterations of 5-hydroxymethylcytosine patterns in differentiating spermatogenic cells are programmed. In ejaculates, a few spermatozoa had high 5-hydroxymethylcytosine level, while in the other ones hydroxymethylation was almost undetectable. The percentage of highly hydroxymethylated (5-hydroxymethylcytosine-positive) spermatozoa varied strongly among individuals. In patients from infertile couples, it was higher than in sperm donors (P<0.0001) and varied in a wider range: 0.12-21.24% versus 0.02-0.46%. The percentage of highly hydroxymethylated spermatozoa correlated strongly negatively with the indicators of good semen quality – normal morphology (r=-0.567, P<0.0001) and normal head morphology (r=-0.609, P<0.0001) – and strongly positively with the indicator of poor semen quality: sperm DNA fragmentation (r=0.46, P=0.001). Thus, the immunocytochemically detected increase of 5hmC in individual spermatozoa is associated with infertility in a couple and with deterioration of sperm parameters. We hypothesize that this increase is not programmed, but represents an induced abnormality and, therefore, it can be potentially used as a novel indicator of semen quality.
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影响因子：
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通讯作者：
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