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

Capsule:
Global levels of sperm DNA methylation are significantly altered through the process of paternal aging.

Authors:
Timothy G. Jenkins, B.S., Kenneth I. Aston, Ph.D., Bradley R. Cairns, Ph.D., Douglas T. Carrell, Ph.D.

Volume 100, Issue 4, Pages 945-951.e2, October 2013

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.

  • Michael Eisenberg

    While the effects of maternal age on the health of offspring are well recognized, the role of the father is less certain. This paper provides important proof that a measurable and relevant factor (sperm methylation patterns) is affected by paternal age. There are several disease known to associated with paternal age. By understanding this relationship better, hopefully we can one day correct it as well.

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