Epigenetic heterogeneity of developmentally important genes in human sperm: implications for assisted reproduction outcome.
Epigenetic heterogeneity of developmentally important genes in human sperm: implications for assisted reproduction outcome.
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DOI：
10.4161/15592294.2014.988063
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发表时间：
2014-12
期刊：
影响因子：
3.7
通讯作者：
Haaf T
中科院分区：
文献类型：
--
作者：
Kuhtz J;Schneider E;El Hajj N;Zimmermann L;Fust O;Linek B;Seufert R;Hahn T;Schorsch M;Haaf T
男性不育症的分子基础尚不清楚，大多数病例仍未解决。精子DNA甲基化模式异常和精液参数受损的关联表明，男性种系表观遗传重编程的紊乱导致了这一问题。到目前为止，关于给定样本中精子的表观遗传异质性以及如何选择最佳精子以成功治疗不孕症的数据很少。限制亚硫酸氢盐稀释对来自可育供体的小精子池进行测序，并没有显示在有和没有形态异常的精子之间异常甲基化印记的发生有显著差异。与标准胞浆内精子注射相比，胞浆内形态学选择精子注射与表观遗传质量的改善无关。对在生育中心就诊的男性精子中2个印迹基因和2个多能性基因的深度亚硫酸盐测序（DBS）显示，在正常精子症和少弱异卵精子症（OAT）的样本中，绝大多数精子等位基因正常（去）甲基化，而表观突变（等位基因甲基化错误）的百分比通常较低（<1%）。然而，DBS允许人们以高精度识别和量化这些罕见的变异。没有导致怀孕的精子样本，特别是在OAT组，与导致活产的样本相比，父亲甲基化的GTL2基因明显更多。所有13个正常精子和13个导致孩子的OAT样本都有<1%的GTL2增殖，而14个正常精子样本中的1个（7%）和14个没有怀孕的OAT样本中的7个（50%）显示1-14%的GTL2增殖。
The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1% GTL2 epimutations, whereas one (7%) of 14 normozoospermic and 7 (50%) of 14 OAT samples without pregnancy displayed 1–14% GTL2 epimutations.