DNA Breakage Copy Number Variations Resulting in Autism/Schizophrenia with Increasing Father's Age

DNA Breakage and Failure of Apoptosis in Sperm as men age


Fertility and Sterility Volume 80, Issue 6 , December 2003, Pages 1420-1430 doi:10.1016/j.fertnstert.2003.04.002 Copyright © 2003 American Society for Reproductive Medicine. Published by Elsevier Science Inc.


Male factor Effects of age on DNA double-strand breaks and apoptosis in human sperm*

1 Narendra P. Singh M.B.B.S., M.S.a, , , Charles H. Muller Ph.D.b and Richard E. Berger M.D.b a Bioengineering, University of Washington, Seattle, Washington, USAb Department of Urology, University of Washington, Seattle, Washington, USA Received 6 February 2003; revised 30 April 2003; accepted 30 April 2003. ; Available online 3 December 2003. AbstractObjectiveThis study was designed to explore the relationship between men's age and DNA damage and apoptosis in human spermatozoa.DesignSemen samples were collected from men between the ages of 20 and 57 years. Sperm DNA double-strand breaks were assessed using the neutral microgel electrophoresis (comet) assay, and apoptosis was estimated using the DNA diffusion assay.SettingAcademic medical center.Patient(s)Sixty-six men aged 20 to 57 years were recruited from infertility laboratory and general populations and consented to donate a semen sample. Recruitment was determined by time and day of analysis; the only exclusions were for azoospermia, prostatitis, or prior cancer therapy.Intervention(s)None.Main outcome measure(s)DNA damage and apoptosis in human sperm.Result(s)Age correlated with an increasing percentage of sperm with highly damaged DNA (range: 0–83%) and tended to inversely correlate with percentage of apoptotic sperm (range: 0.3%–23%). For example, percentage of sperm with highly damaged DNA, comet extent, DNA break number, and other comet measures was statistically significantly higher in men aged 36–57 years than in those aged 20–35 years, but percentage apoptosis was statistically significantly lower in the older group. Semen analysis showed percentage motility to be significantly higher in younger age groups.Conclusion(s)This study clearly demonstrates an increase in sperm double-stranded DNA breaks with age. Our findings also suggest for the first time an age-related decrease in human sperm apoptosis. These novel findings may indicate deterioration of healthy sperm cell selection process with age. Author Keywords: DNA double-strand breaks; apoptosis; human sperm; aging; Comet assay Corresponding author. Reprint requests: Narendra P. Singh, M.B.B.S., M.S., Department of Bioengineering, Box 357962, University of Washington, , Seattle, Washington 98195-7962, , USA (FAX: 206-685-2060).*1 Supported by the Paul G. Allen Foundation for Medical Research.
Labels: apoptosis, sperm DNA double-strand breaks