Thursday, May 31, 2007

Frequency of XY sperm 10 percent higher among fathers of Klinefelters in 30s, 31 percent highers in 40s, 160 percent higher in fathers in their 50s

Am. J. Hum. Genet., 69:1046-1054, 2001
© 2001 by The American Society of Human Genetics. All rights reserved.


Frequency of XY Sperm Increases with Age in Fathers of Boys with Klinefelter Syndrome
1Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA, and 2School of Public Health, University of California, Berkeley

Received June 18, 2001; accepted for publication August 13, 2001; electronically published October 1, 2001.

With increasing availability of drugs for impotence and advanced reproductive technologies for the treatment of subfertility, more men are fathering children at advanced ages. We conducted a study of the chromosomal content of sperm of healthy men aged 2457 years to (a) determine whether father's age was associated with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y, disomy 21, and sperm diploidy, and (b) examine the association between the frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH (10,000 sperm per donor). Paternal age was significantly correlated with the sex ratio of sperm (Y/X; P = .006) and with the frequency of XY sperm (P = .02), with a clear trend with age by decades (P < .006). Compared with fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000), the frequencies of XY sperm were 10% higher among fathers in their 30s, 31% higher among those in their 40s, and 160% higher among those in their 50s (95% CI 69%300%). However, there was no evidence for age effects on frequencies of sperm carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The frequencies of disomy 21 sperm were significantly associated with sex-chromosomal aneuploidy (P = .04)in particular, with disomy X (P = .004), but disomy 21 sperm did not preferentially carry either sex chromosome. These findings suggest that older fathers produce higher frequencies of XY sperm, which may place them at higher risk of fathering boys with Klinefelter syndrome, and that age effects on sperm aneuploidy are chromosome specific.

* The first two authors contributed equally to this work.
Present affiliation: Department of Psychiatry, California Pacific Medical Center, San Francisco.

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