Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents.

Fertil Steril. 2004 Apr;81(4):925-43. Links
Sloter E, Nath J, Eskenazi B, Wyrobek AJ.
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.




http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&list_uids=15066442&cmd=Retrieve&indexed=google
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Sex chromosomal nondisjunction increased with age in both human and rodent male germ cells. Both human and rodent data showed age-related increases in the number of sperm with chromosomal breaks and fragments and suggest that postmeiotic cells are particularly vulnerable to the effects of aging. Translocation frequencies increased with age in murine spermatocytes, at rates comparable to mouse and human somatic cells. Age-related mechanisms of induction may include accumulation of environmental damage, reduced efficiency of DNA repair, increased genomic instability, genetic factors, hormonal influences, suppressed apoptosis, or decreased effectiveness of antioxidants and micronutrients.

CONCLUSION(S): The weight of evidence suggests that the increasing trend toward fathering at older ages may have significant effects on the viability and genetic health of human pregnancies and offspring, primarily as a result of structural chromosomal aberrations in sperm.

PMID: 15066442 [PubMed - indexed

The Effect of Male Age on Sperm DNA Damage

1: Hum Reprod. 2007 Jan;22(1):180-7. Epub 2006 Oct 19. Links
The effects of male age on sperm DNA damage in healthy non-smokers.Schmid TE, Eskenazi B, Baumgartner A, Marchetti F, Young S, Weldon R, Anderson D, Wyrobek AJ.
Lawrence Livermore National Laboratory, Livermore, CA, USA.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

PMID: 17053003 [PubMed - indexed for MEDLINE]