Influence of deoxyribonucleic acid damage on fertilization and pregnancy
Date
2004
Authors
Henkel R.
Hajimohammad M.
Stalf T.
Hoogendijk C.
Mehnert C.
Menkveld R.
Gips H.
Schill W.-B.
Kruger T.F.
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Journal ISSN
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Abstract
Objective To investigate sperm DNA damage in relation to fertilization and pregnancy. Design Prospective study. Setting The Institute of Reproductive Medicine, Giessen, Germany. Patient(s) Semen collected from 249 patients attending the IVF program. Main outcome measure(s) The percentage of terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling- (TUNEL-), Fas-, and annexin-V-positive sperm and the proportion of green-fluorescing sperm in the acridine orange stain was determined and correlated with sperm concentration, motility, fertilization, and pregnancy. Result(s) Significant correlations with the concentration of motile sperm were only found for the acridine orange stain (before and after sperm separation) and for the TUNEL assay (after sperm separation). Moreover, patients whose sperm had a high percentage of DNA fragmentations showed significantly lower pregnancy rates (TUNEL assay: 19.05% vs. 34.65%; acridine orange stain: 24.58% vs. 37.93%). The apoptosis parameters (annexin V binding and Fas expression) showed no statistically significant differences. Conclusions Our data clearly demonstrate that DNA fragmentation, as determined by the TUNEL assay, is predictive for pregnancy in IVF. This implies that spermatozoa with DNA fragmentation can still fertilize an oocyte but that when paternal genes are "switched on," further embryonic development stops, resulting in failed pregnancy. It seems that, at least in the patients we analyzed, apoptosis in the sperm does not play a role for fertilization. This would imply that DNA fragmentation in human spermatozoa is caused by external factors, such as reactive oxygen species, rather than by apoptosis. © 2004 by American Society for Reproductive Medicine.
Description
Keywords
acridine orange, DNA, DNA fragment, Fas antigen, green fluorescent protein, lipocortin 5, apoptosis, article, correlation analysis, DNA damage, fertilization, fertilization in vitro, human, human cell, infertility, nick end labeling, oocyte, prediction, pregnancy, pregnancy rate, priority journal, prospective study, protein binding, protein expression, sperm, spermatozoon, spermatozoon density, spermatozoon motility, statistical significance, Acridine Orange, Annexin A5, Antigens, CD95, Apoptosis, DNA Damage, Female, Fertilization in Vitro, Fluorescent Dyes, Humans, In Situ Nick-End Labeling, Male, Pregnancy, Pregnancy Rate, Sperm Motility, Spermatozoa, Staining and Labeling, Treatment Failure
Citation
Fertility and Sterility
81
4
81
4