Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

Full Abstract

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

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Author information

Author/s: Wyrobek, A J (AJ); Eskenazi, B (B); Young, S (S); Arnheim, N (N); Tiemann-Boege, I (I); Jabs, E W (EW); Glaser, R L (RL); Pearson, F S (FS); Evenson, D (D);

Affiliation: Biosciences Directorate, Lawrence Livermore National Laboratory, 1 Cyclotron Road, Livermore, CA 94550, USA. ajwyrobek(-atsign-)gmail.com

Grants: GM 36745 (Agency:NIGMS NIH HHS) ; P42 ES 04705 (Agency:NIEHS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2006-Jun; vol 103 (issue 25) : pp 9601-6

Dates: Created 2006/06/21; Completed 2006/08/14; Revised 2008/11/20;

PMID: 16766665, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Achondroplasia - genetics
Acrocephalosyndactylia - genetics
Adult
Aged
Aged, 80 and over
Aging - genetics; physiology
Aneuploidy
Chromatin - genetics; physiology

DNA Damage
Diploidy
Humans
Male
Middle Aged
Mutagenesis - genetics
Mutation - genetics
Spermatozoa - abnormalities; metabolism

Associated Chemicals: Chromatin (0)

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