ADVANCING PATERNAL AGE IS ASSOCIATED WITH A GRADUAL AND SIGNIFICANT INCREASE IN THE RISK OF FATHERING CHILDREN WITH VARIOUS CHROMOSOMAL DEFECTS

1: Fertil Steril. 2007 Apr 10; [Epub ahead of print] Links
Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age.Sloter ED, Marchetti F, Eskenazi B, Weldon RH, Nath J, Cabreros D, Wyrobek AJ.
Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, California; Genetics and Developmental Biology Program, West Virginia University, Morgantown, West Virginia; Department of Epidemiology, School of Public Health, University of California, Berkeley, California.

OBJECTIVE: To investigate the association between male age and the frequency of sperm with de novo structural chromosomal abnormalities. DESIGN: Semen specimens collected from two groups of 10 healthy, nonsmoking men, aged 22-28 and 65-80 years, were analyzed with the use of a multicolor fluorescence in situ hybridization assay for detecting breaks, segmental duplications and deletions, and aneuploidy and diploidy involving chromosome 1. SETTING: Healthy volunteer workers and retirees from a government research environment. MAIN OUTCOME MEASURE: Sperm carrying numerical and structural chromosomal abnormalities. RESULT(S): We detected significant increases in the frequency of sperm carrying breaks and segmental duplications and deletions of chromosome 1 among older men compared with younger men. Older men carried twice the frequency of sperm with segmental duplications and deletions of chromosome 1. The frequency of sperm carrying breaks within the 1q12 fragile-site region nearly doubled in older men. In contrast to female gametes, there was no effect of age on the frequency of sperm with numerical chromosomal abnormalities. CONCLUSION: Our findings suggest that advancing male age is associated with a gradual and significant increase in the risk of fathering children with various chromosomal defects such as segmental aneusomy syndromes.

PMID: 17433321 [PubMed - as supplied by publisher]




Overall, our findings suggest that the increasing trend of fathering children at older ages predicts a greater incidence of abnormal reproductive outcomes and genetic diseases of paternal origin resulting from chromosomal breaks, duplications, and deletions, assuming that sperm with these abnormalities are as likely to fertilize as normal sperm. A broad spectrum of abnormal reproductive outcomes was associated with the types of chromosomal defects that we detected in sperm, such as spontaneous abortions, neonatal death, birth defects, developmental delay, and mental retardation. Specifically, our data predict that advancing paternal age may be associated with an increased risk for offspring carrying the 1p36 deletion syndrome. Aging men are also predicted to be at increased risk for transmitting the 1p36 duplication product to offspring, although the health consequences associated with duplications are less understood than those of deletions. Our observed association of age with the frequency of sperm with a 1q12 breakage may have significant clinical implications, given the general concurrence between genomic fragile sites and de novo breakpoint locations of chromosomal rearrangements in spontaneous abortions and newborns (83).