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父系衰老与个体内精子全基因组 5-甲基胞嘧啶和 5-羟甲基胞嘧啶水平的相关变化。

Paternal aging and associated intraindividual alterations of global sperm 5-methylcytosine and 5-hydroxymethylcytosine levels.

机构信息

Department of Surgery, Andrology and IVF Laboratories, University of Utah School of Medicine, Salt Lake City, Utah.

出版信息

Fertil Steril. 2013 Oct;100(4):945-51. doi: 10.1016/j.fertnstert.2013.05.039. Epub 2013 Jun 27.

DOI:10.1016/j.fertnstert.2013.05.039
PMID:23809503
Abstract

OBJECTIVE

To evaluate the relative intraindividual changes in sperm 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels associated with age and to compare the levels of 5-hmC in mature human sperm to blood DNA.

DESIGN

Prospective research study.

SETTING

University-based andrology and in vitro fertilization (IVF) laboratory.

PATIENT(S): Fifteen known fertile sperm donors, 22 other known fertile controls, and 41 male blood donors from a general population tissue bank.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Measurements of global 5-mC and 5-hmC levels via an enzyme-linked immunosorbent assay (ELISA)-based assay.

RESULT(S): Global sperm 5-mC levels exhibit a statistically significant increase with age, and a similar trend was seen in 5-hmC levels. On average, in the age ranges we analyzed, 5-mC increased by 1.76% per year, and 5-hmC, though more variable, increased by approximately 5% per year. Additionally, we found that 5-hmC levels in sperm are 32.59% of that found in blood DNA.

CONCLUSION(S): Global sperm DNA methylation patterns are stable over short periods of time but increase with age, which raises important questions regarding the risks of advanced paternal age. Additionally, as we would predict for a transcriptionally quiescent cell type, 5-hmC levels are statistically significantly lower in human sperm than in blood DNA.

摘要

目的

评估与年龄相关的精子 5- 甲基胞嘧啶(5-mC)和 5- 羟甲基胞嘧啶(5-hmC)水平的个体内相对变化,并比较成熟人类精子和血液 DNA 中的 5-hmC 水平。

设计

前瞻性研究。

地点

大学基础男科和体外受精(IVF)实验室。

患者

15 名已知的有生育能力的精子供体、22 名其他已知的有生育能力的对照者和 41 名来自一般人群组织库的男性献血者。

干预

无。

主要观察指标

通过酶联免疫吸附测定(ELISA)检测全局 5-mC 和 5-hmC 水平。

结果

全局精子 5-mC 水平随年龄呈统计学显著增加,5-hmC 水平也呈现类似趋势。在我们分析的年龄范围内,平均而言,5-mC 每年增加 1.76%,5-hmC 虽然更具变异性,但每年增加约 5%。此外,我们发现精子中的 5-hmC 水平是血液 DNA 中的 32.59%。

结论

精子 DNA 甲基化模式在短时间内是稳定的,但随年龄增长而增加,这引发了关于高龄父亲风险的重要问题。此外,正如我们对转录静止细胞类型的预测,人类精子中的 5-hmC 水平在统计学上显著低于血液 DNA。

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