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

Objective: To review evidence regarding the effects of male age on germinal and heritable chromosomal abnormalities using available human and rodent studies and to evaluate possible underlying mechanisms. Design: Review of English language-published research using MEDLINE database, excluding case reports and anecdotal data. Result(s): There was little evidence from offspring or germ cell studies for a generalized male age effect on autosomal aneuploidy, except in rodents. 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. (C) 2004 by American Society for Reproductive Medicine.