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Regular Article |
a Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063
b Assisted Conception Unit, Birmingham Women's Hospital, Birmingham B15 2TG, United Kingdom
c Department of Animal Biology, University of Modena and Reggio Emilia, Modena 41100, Italy
d Department of Obstetrics and Gynecology, University Hospital of Geneva, 1211 Geneva 14, Switzerland
e Institute of Biology and Genetics, University of Ancona, Ancona 60131, Italy
Numerous studies have shown the presence of DNA strand breaks in human ejaculated spermatozoa. The nature of this nuclear anomaly and its relationship to patient etiology is however poorly understood. The aim of this study was to investigate the relationship between nuclear DNA damage, assessed using the TUNEL assay and a number of key apoptotic markers, including Fas, Bcl-x, and p53, in ejaculated human spermatozoa from men with normal and abnormal semen parameters. We also determined the nature of the DNA damage by examining the percentage of ejaculated spermatozoa exhibiting DNA damage using the comet assay and by challenging sperm chromatin to attack by micrococcal nuclease S7 and DNase I. We show that TUNEL positivity and apoptotic markers do not always exist in unison; however, semen samples that had a low sperm concentration and poor morphology were more likely to show high levels of TUNEL positivity and Fas and p53 expression. In addition, the DNA damage in ejaculated human sperm is represented by both single- and double-stranded DNA breaks, and access to the DNA is restricted by the compacted nature of ejaculated spermatozoa. This DNA protection is poorer in men with abnormal semen parameters. We propose that the presence of DNA damage is not directly linked to an apoptotic process occurring in spermatozoa and arises due to problems in the nuclear remodeling process. Subsequently, the presence of apoptotic proteins in ejaculated spermatozoa may be linked to defects in cytoplasmic remodeling during the later stages of spermatogenesis.
1 This work was supported in part by a grant from the Birmingham Women's Hospital Research and Development Fund and from the Italian Ministero della Ricerca Scientifica e Tecnologica (MURST).
2 Correspondence: Denny Sakkas, Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208063, New Haven, CT 06520-8063. FAX: 203 785 7134; denny.sakkas{at}yale.edu
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