The effects of male age on sperm DNA damage in healthy non-smokers

Schmid, T; Eskenazi, B; Baumgartner, A; Marchetti, F; Young, S; Weldon, R; Anderson, D; Wyrobek, A

doi:10.1093/humrep/del338

Title: The effects of male age on sperm DNA damage in healthy non-smokers

Journal Article · Wed Mar 08 00:00:00 EST 2006 · Human Reproduction

DOI:https://doi.org/10.1093/humrep/del338· OSTI ID:902230

Schmid, T; Eskenazi, B; Baumgartner, A; Marchetti, F; Young, S; Weldon, R; Anderson, D; Wyrobek, A

The trend for men to have children at older ages raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (age: 22-80) with no known fertility problems using the sperm Comet analyses. The average percent of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, p=0.006); but there was no age association for damage measured under neutral conditions (p=0.7). Men who consumed >3 cups coffee per day had {approx}20% higher % tail DNA under neutral but not alkaline conditions compared to men who consumed no caffeine (p=0.005). Our findings indicate that (a) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks, and (b) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization increasing the risks for developmental defects and genetic diseases among offspring.

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Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: W-7405-ENG-48

OSTI ID:: 902230

Report Number(s):: UCRL-JRNL-219655; TRN: US200717%%210

Journal Information:: Human Reproduction, Vol. 22, Issue 1; ISSN 0268-1161

Country of Publication:: United States

Language:: English

References (57)

Human sperm DNA integrity assessed by the Comet and ELISA assays M. Hughes, C. Mutagenesis, Vol. 14, Issue 1 https://doi.org/10.1093/mutage/14.1.71	journal	January 1999
Antioxidant intake is associated with semen quality in healthy men Eskenazi, B.; Kidd, S. A.; Marks, A. R. Human Reproduction, Vol. 20, Issue 4 https://doi.org/10.1093/humrep/deh725	journal	April 2005
Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo Harrouk, Wafa; Codrington, Alexis; Vinson, Robert Mutation Research/DNA Repair, Vol. 461, Issue 3 https://doi.org/10.1016/S0921-8777(00)00053-7	journal	November 2000
Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors Shi, Q.; Martin, R. H. Cytogenetic and Genome Research, Vol. 90, Issue 3-4 https://doi.org/10.1159/000056773	journal	January 2000
Flavonoids modulate Comet assay responses to food mutagens in human lymphocytes and sperm Anderson, D.; Dobryńska, M. M.; Başaran, N. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 402, Issue 1-2 https://doi.org/10.1016/S0027-5107(97)00306-0	journal	June 1998
Nicking of Rat Spermatid and Spermatozoa DNA: Possible Involvement of DNA Topoisomerase II McPherson, Sandra M. G.; Longo, Frank J. Developmental Biology, Vol. 158, Issue 1 https://doi.org/10.1006/dbio.1993.1173	journal	July 1993
Assessment of DNA damage and its modulation by dietary and genetic factors in smokers using the Comet assay: a biomarker model Glei, M.; Habermann, N.; Osswald, K. Biomarkers, Vol. 10, Issue 2-3 https://doi.org/10.1080/13547500500138963	journal	January 2005
Germ cell suicide: new insights into apoptosis during spermatogenesis Print, Cristin G.; Loveland, Kate Lakoski BioEssays, Vol. 22, Issue 5 https://doi.org/10.1002/(SICI)1521-1878(200005)22:5<423::AID-BIES4>3.0.CO;2-0	journal	April 2000
The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios Spano, M.; Kolstad, A. H.; Larsen, S. B. Human Reproduction, Vol. 13, Issue 9 https://doi.org/10.1093/humrep/13.9.2495	journal	September 1998
Long-term effects of delayed parenthood Tarin, J. J.; Brines, J.; Cano, A. Human Reproduction, Vol. 13, Issue 9 https://doi.org/10.1093/humrep/13.9.2371	journal	September 1998
The origins, patterns and implications of human spontaneous mutation Crow, James F. Nature Reviews Genetics, Vol. 1, Issue 1 https://doi.org/10.1038/35049558	journal	October 2000
A wilcoxon-type test for trend Cuzick, Jack Statistics in Medicine, Vol. 4, Issue 1 https://doi.org/10.1002/sim.4780040112	journal	January 1985
Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations Marchetti, Francesco; Lowe, Xiu; Bishop, Jack Environmental and Molecular Mutagenesis, Vol. 30, Issue 4 https://doi.org/10.1002/(SICI)1098-2280(1997)30:4<410::AID-EM6>3.0.CO;2-M	journal	January 1997
Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm Wyrobek, A. J.; Eskenazi, B.; Young, S. Proceedings of the National Academy of Sciences, Vol. 103, Issue 25 https://doi.org/10.1073/pnas.0506468103	journal	June 2006
Smoking and High Plasma Triglyceride Levels as Risk Factors for Oxidative DNA Damage in the Korean Population Park, Eunju; Kang, Myung-Hee Annals of Nutrition and Metabolism, Vol. 48, Issue 1 https://doi.org/10.1159/000075083	journal	January 2004
Transient DNA Strand Breaks During Mouse and Human Spermiogenesis:New Insights in Stage Specificity and Link to Chromatin Remodeling1 Marcon, Ludovic; Boissonneault, Guylain Biology of Reproduction, Vol. 70, Issue 4 https://doi.org/10.1095/biolreprod.103.022541	journal	April 2004
Delayed parenting: Is delayed childbearing a good thing? Lansac, J. Human Reproduction, Vol. 10, Issue 5 https://doi.org/10.1093/oxfordjournals.humrep.a136086	journal	May 1995
The association of age and semen quality in healthy men Eskenazi, B. Human Reproduction, Vol. 18, Issue 2 https://doi.org/10.1093/humrep/deg107	journal	February 2003
Linear increase of structural and numerical chromosome 9 abnormalities in human sperm regarding age Bosch, Mercè; Rajmil, Osvaldo; Egozcue, Josep European Journal of Human Genetics, Vol. 11, Issue 10 https://doi.org/10.1038/sj.ejhg.5201049	journal	September 2003
Apoptosis as a mechanism of germ cell loss in elderly men Brinkworth, M. H.; Weinbauer, G. F.; Bergmann, M. International Journal of Andrology, Vol. 20, Issue 4 https://doi.org/10.1046/j.1365-2605.1997.00056.x	journal	August 1997
The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development Morris, I. D. Human Reproduction, Vol. 17, Issue 4 https://doi.org/10.1093/humrep/17.4.990	journal	April 2002
Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease Aitken, R. John; Baker, Mark A.; Sawyer, Dennis Reproductive BioMedicine Online, Vol. 7, Issue 1 https://doi.org/10.1016/S1472-6483(10)61730-0	journal	January 2003
The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Duty, Susan M.; Singh, Narendra P.; Silva, Manori J. Environmental Health Perspectives, Vol. 111, Issue 9 https://doi.org/10.1289/ehp.5756	journal	July 2003
Sperm DNA damage and cancer treatment1 Morris, Ian D. International Journal of Andrology, Vol. 25, Issue 5 https://doi.org/10.1046/j.1365-2605.2002.00372.x	journal	October 2002
Photoinduction of strand scission in DNA by uric acid and Cu(II) Shamsi, Farrukh A.; Hadi, S. M. Free Radical Biology and Medicine, Vol. 19, Issue 2 https://doi.org/10.1016/0891-5849(95)00004-H	journal	August 1995
Repair of UV damage to DNA of implantation-stage mouse embryos in vitro Pedersen, R. A.; Cleaver, J. E. Experimental Cell Research, Vol. 95, Issue 2 https://doi.org/10.1016/0014-4827(75)90548-0	journal	October 1975
Effects of male age on semen quality and fertility: a review of the literature Kidd, Sharon A.; Eskenazi, Brenda; Wyrobek, Andrew J. Fertility and Sterility, Vol. 75, Issue 2 https://doi.org/10.1016/S0015-0282(00)01679-4	journal	February 2001
Recommendations for conducting the in vivo alkaline Comet assay Hartmann, A. Mutagenesis, Vol. 18, Issue 1 https://doi.org/10.1093/mutage/18.1.45	journal	January 2003
Cross-species sperm-FISH assays for chemical testing and assessing paternal risk for chromosomally abnormal pregnancies Wyrobek, Andrew J.; Schmid, Thomas E.; Marchetti, Francesco Environmental and Molecular Mutagenesis, Vol. 45, Issue 2-3 https://doi.org/10.1002/em.20121	journal	January 2005
Parental Age at Child's Birth and Son's Risk of Prostate Cancer: The Framingham Study Zhang, Y.; Kreger, B. E.; Dorgan, J. F. American Journal of Epidemiology, Vol. 150, Issue 11 https://doi.org/10.1093/oxfordjournals.aje.a009947	journal	December 1999
Correlation between sperm motility and sperm chromatin structure assay parameters Giwercman, Aleksander; Richthoff, Jonas; Hjøllund, Henrik Fertility and Sterility, Vol. 80, Issue 6 https://doi.org/10.1016/S0015-0282(03)02212-X	journal	December 2003
Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg. Generoso, W. M.; Cain, K. T.; Krishna, M. Proceedings of the National Academy of Sciences, Vol. 76, Issue 1 https://doi.org/10.1073/pnas.76.1.435	journal	January 1979
The Paternal-Age Effect in Apert Syndrome Is Due, in Part, to the Increased Frequency of Mutations in Sperm Glaser, Rivka L.; Broman, Karl W.; Schulman, Rebecca L. The American Journal of Human Genetics, Vol. 73, Issue 4 https://doi.org/10.1086/378419	journal	October 2003
Detection of Deoxyribonucleic Acid Fragmentation in Human Sperm: Correlation with Fertilization in Vitro1 Sun, Jian-Guo; Jurisicova, Andrea; Casper, Robert F. Biology of Reproduction, Vol. 56, Issue 3 https://doi.org/10.1095/biolreprod56.3.602	journal	March 1997
Chromatin fluorescence characteristics and standard semen analysis parameters: correlations observed in andrology testing among 136 males referred for infertility evaluation Sills, E. Scott; Fryman, Julie T.; Perloe, M. Journal of Obstetrics and Gynaecology, Vol. 24, Issue 1 https://doi.org/10.1080/01443610310001620369	journal	January 2004
Modulating effects of flavonoids on food mutagens in human blood and sperm samples in the Comet assay Anderson, Diana; Basaran, Nur?en; Dobrzy?ska, Malgorzata M. Teratogenesis, Carcinogenesis, and Mutagenesis, Vol. 17, Issue 2 https://doi.org/10.1002/(SICI)1520-6866(1997)17:2<45::AID-TCM1>3.0.CO;2-E	journal	January 1997
Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study de La Rochebrochard, Elise; Thonneau, Patrick Human Reproduction, Vol. 17, Issue 6 https://doi.org/10.1093/humrep/17.6.1649	journal	June 2002
Effects of age on DNA double-strand breaks and apoptosis in human sperm Singh, Narendra P.; Muller, Charles H.; Berger, Richard E. Fertility and Sterility, Vol. 80, Issue 6 https://doi.org/10.1016/j.fertnstert.2003.04.002	journal	December 2003
Individuality of DNA denaturation patterns in human sperm as measured by the sperm chromatin structure assay Evenson, Donald P.; Jost, Lorna K.; Baer, Rebecca K. Reproductive Toxicology, Vol. 5, Issue 2 https://doi.org/10.1016/0890-6238(91)90039-I	journal	January 1991
Effect of Antioxidant Intake on Sperm Chromatin Stability in Healthy Nonsmoking Men Silver, E. W. Journal of Andrology, Vol. 26, Issue 4 https://doi.org/10.2164/jandrol.04165	journal	July 2005
Cigarette smoking and aneuploidy in human sperm Shi, Qinghua; Ko, Evelyn; Barclay, Leona Molecular Reproduction and Development, Vol. 59, Issue 4 https://doi.org/10.1002/mrd.1048	journal	January 2001
Beckwith-Wiedemann syndrome and assisted reproduction technology (ART) Maher, E. R. Journal of Medical Genetics, Vol. 40, Issue 1 https://doi.org/10.1136/jmg.40.1.62	journal	January 2003
Clinical aspects of sperm DNA fragmentation detection and male infertility Evenson, Donald P.; Wixon, Regina Theriogenology, Vol. 65, Issue 5 https://doi.org/10.1016/j.theriogenology.2005.09.011	journal	March 2006
The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect Tiemann-Boege, I.; Navidi, W.; Grewal, R. Proceedings of the National Academy of Sciences, Vol. 99, Issue 23 https://doi.org/10.1073/pnas.232568699	journal	October 2002
Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa Barroso, Gerardo; Morshedi, Mahmood; Oehninger, Sergio Human Reproduction, Vol. 15, Issue 6 https://doi.org/10.1093/humrep/15.6.1338	journal	June 2000
Repair of the ultraviolet-irradiated male genome in fertilized mouse eggs Brandriff, B.; Pedersen, R. Science, Vol. 211, Issue 4489 https://doi.org/10.1126/science.7466400	journal	March 1981
DNA Damage in Human and Mouse Spermatozoa after In Vitro-Irradiation Assessed by the Comet Assay Haines, Grant; Marples, Brian; Daniel, Paul Reproductive Toxicology, 79–93 https://doi.org/10.1007/978-1-4899-0089-0_10	book	January 1998
Smoking cigarettes is associated with increased sperm disomy in teenage men11This manuscript has been reviewed in accordance with the policy of the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for their use.88This study was performed in part under the auspices of the U.S. DOE by the Lawrence Livermore National Laboratory under contract W-7405-ENG-48 with support from U.S. Environmental Protection Agency IA DW8 9936308 and Tobacco-Related Disease Research Program 3RT-0223. Recruitment, field work, and conventional semen analyses were supported by the Czech Ministry of the Environment (Teplice Program), the U.S. Environmental Protection Agency/U.S. AID and CEC (PHARE II, EC/HEA/18/CZ), and U.S. Environmental Protection Agency R820968 (DPE) and CR820076. Rubes, Jiřı́; Lowe, Xiu; Moore, Dan Fertility and Sterility, Vol. 70, Issue 4 https://doi.org/10.1016/S0015-0282(98)00261-1	journal	October 1998
Effects of cigarette smoking on sperm plasma membrane integrity and DNA fragmentation Belcheva, Antoaneta; Ivanova-Kicheva, Maria; Tzvetkova, Petia International Journal of Andrology, Vol. 27, Issue 5 https://doi.org/10.1111/j.1365-2605.2004.00486.x	journal	October 2004
Paternally Transmitted Chromosomal Aberrations in Mouse Zygotes Determine Their Embryonic Fate1 Marchetti, Francesco; Bishop, Jack B.; Cosentino, Lidia Biology of Reproduction, Vol. 70, Issue 3 https://doi.org/10.1095/biolreprod.103.023044	journal	March 2004
Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients Kodama, Hideya; Yamaguchi, Raizo; Fukuda, Jun Fertility and Sterility, Vol. 68, Issue 3 https://doi.org/10.1016/S0015-0282(97)00236-7	journal	September 1997
Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques Larson, K. L. Human Reproduction, Vol. 15, Issue 8 https://doi.org/10.1093/humrep/15.8.1717	journal	August 2000
Relative Susceptibilities of Male Germ Cells to Genetic Defects Induced by Cancer Chemotherapies Wyrobek, A. J. Journal of the National Cancer Institute Monographs, Vol. 2005, Issue 34 https://doi.org/10.1093/jncimonographs/lgi001	journal	March 2005
Effect of age on testicular germ cell apoptosis and sperm aneuploidy in MF-1 mice Brinkworth, M. H.; Schmid, T. E. Teratogenesis, Carcinogenesis, and Mutagenesis, Vol. 23, Issue S2 https://doi.org/10.1002/tcm.10085	journal	January 2003
Assessment of DNA integrity and morphology of ejaculated spermatozoa from fertile and infertile men before and after cryopreservation Donnelly, E. T. Human Reproduction, Vol. 16, Issue 6 https://doi.org/10.1093/humrep/16.6.1191	journal	June 2001
Possible consequences of performing intracytoplasmic sperm injection (ICSI) with sperm possessing nuclear DNA damage Sakkas, Denny; Manicardi, GianCarlo; Bizzaro, Davide Human Fertility, Vol. 3, Issue 1 https://doi.org/10.1080/1464727002000198651	journal	January 2000
Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents Sloter, Eddie; Nath, Joginder; Eskenazi, Brenda Fertility and Sterility, Vol. 81, Issue 4 https://doi.org/10.1016/j.fertnstert.2003.07.043	journal	April 2004

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BEVERAGES
CAFFEINE
CHILDREN
CHROMOSOMAL ABERRATIONS
DEFECTS
DISEASES
DNA
DNA DAMAGES
ELECTROPHORESIS
FERTILITY
FERTILIZATION
GENE MUTATIONS
GENETICS
MALES
MUTATIONS
SPERMATOZOA

Title: The effects of male age on sperm DNA damage in healthy non-smokers

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