Decreased fecundity and sperm DNA methylation patterns.
Decreased fecundity and sperm DNA methylation patterns.
复制标题
DOI：
10.1016/j.fertnstert.2015.09.013
复制
发表时间：
2016-01
影响因子：
6.7
通讯作者：
Carrell DT
中科院分区：
文献类型：
--
作者：
Jenkins TG;Aston KI;Meyer TD;Hotaling JM;Shamsi MB;Johnstone EB;Cox KJ;Stanford JB;Porucznik CA;Carrell DT
探讨精子表观遗传模式与生育力的关系。犹他州大学利用HOPE研究收集的精液样本对试图怀孕的夫妇进行的前瞻性研究。在124份精液样本中分析了与生育力相关的学术男性学和IVF实验室DNA甲基化改变。分析了27份来自试图怀孕2个月内怀孕的夫妇的精液样本和29份来自12个月内无法怀孕的夫妇的精液样本，以确定感兴趣的区域。一个也没有。精子DNA甲基化差异的全基因组评估和标准精液分析。在研究时间2个月内妊娠的患者与12个月内未妊娠的患者之间，未观察到精子计数、精子形态或精液量的差异。然而，使用来自人类甲基化450k阵列分析的数据，我们确实在“未能怀孕”组中鉴定出2个甲基化显著降低（FDR <0.01）的基因组区域和3个甲基化显著增加的基因组区域。有趣的是，仅有的两个甲基化降低与生育力降低相关的位点是已知在精子中表达的密切相关的基因，HSPA1L和HSPA1B。我们的数据表明，有基因组位点的DNA甲基化改变与生殖力下降。因此，我们已经确定了候选位点，为未来的研究，以验证这些结果，并调查改变精子甲基化和生育力下降之间的因果关系或贡献关系。
To evaluate the relationship between epigenetic patterns in sperm and fecundity. Prospective study of couples trying to conceive, utilizing semen samples collected through the HOPE study, at the University of Utah. Academic Andrology and IVF Laboratory DNA methylation alterations associated with fecundity were analyzed in 124 semen samples. 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months were analyzed to identify regions of interest. None. Genome-wide assessment of differential sperm DNA methylation and standard semen analysis. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the Human Methylation 450k array analysis we did identify 2 genomic regions with significantly decreased (FDR <0.01) methylation and 3 genomic regions with significantly increased methylation in the “failure-to-conceive” group. Interestingly, the only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B. Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.