Cited by 189Sperm and Testicular FunctionReproductive Biology and FertilityReproductive biology and impacts on aquatic species

Impact of sperm morphology on DNA damage caused by oxidative stress induced by β-nicotinamide adenine dinucleotide phosphate

Open access
Said, Tamer M., Agarwal, Ashok, Sharma, Rakesh K., Thomas, Anthony J., Sikka, Suresh C.·2005·Fertility and Sterility

Abstract

Objective To investigate the role of DNA damage induced by beta-nicotinamide adenine dinucleotide phosphate (NADPH) in human spermatozoa. Design Prospective controlled study. Setting Male infertility clinic at the Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s) Twenty-eight men undergoing infertility screening. Intervention(s) Chemiluminescence assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay coupled flow cytometry after incubating mature and immature sperm separated by density gradient with 5 mM NADPH for 0, 3, and 24 hours. Main outcome measure(s) Reactive oxygen species (ROS) generation (10(6) counted photons per minute/10(6) sperm) and percentage of spermatozoa with fragmented DNA. Result(s) Immature sperm from teratozoospermic semen samples were characterized by a statistically significant presence of cytoplasmic residues in the mid-piece when compared with mature normozoospermic samples. Increased ROS production was observed in spermatozoa rich in cytoplasmic residues that showed a statistically significant positive correlation with sperm DNA damage in a time-dependent manner. Conclusion(s) Immature sperm contain high nicotinamide adenine dinucleotide phosphate (NADPH) in cytoplasmic droplets, but it has not yet been clear whether abnormal sperm morphology plays any role in sperm DNA damage induced by oxidative stress. Our data support the role of NAPDH in ROS-mediated sperm DNA damage and suggest that abnormal sperm morphology combined with elevated ROS production may serve as a useful indicator of potential damage to sperm DNA.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.fertnstert.2004.06.056

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Causes for increased oxidative stress in teratozoospermic men include the increase of MDA, lipid peroxidation, iron, and NADPH, which is positively correlated with damage to sperm DNA.

    “Causes for increased oxidative stress in teratozoospermic men include the increase of MDA (malondialdehyde), lipid peroxidation, iron, and NADPH (nicotinamide adenine dinucleotide phosphate), which is positively correlated with the damage to sperm DNA (74,75).”

    From Isolated teratozoospermia: revisiting its relevance in male infertility: a narrative review (2024) · cites this paper as [75]

    The Discussion (page unavailable) says that cytoplasmic residues in immature sperm generate NADPH, which stimulates ROS production, and links these sperm to oxidative DNA damage in teratozoospermic samples. The cited passages do not establish increased MDA, lipid peroxidation, or iron as causes of oxidative stress in these men, or correlate those factors with sperm DNA damage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 46

  1. Oehninger S, Blackmore P, Mahony M, Hodgen G. Effects of hydrogen peroxide on human spermatozoa. J Assist Reprod Genet 1995;12:41-47.
  2. de Lamirande E, Harakat A, Gagnon C. Human sperm capacitation induced by biological fluids and progesterone, but not by NADH or NADPH, is associated with the production of superoxide anion. J Androl 1997;19:215-25.
  3. Rivlin J, Mendel J, Rubinstein S, Etkovitz N, Breitbart H. Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol Reprod 2004;70:518 -22.
  4. Thundathil J, de Lamirande E, Gagnon C. Nitric oxide regulates the phosphorylation of the threonine-glutamine-tyrosine motif in proteins of human spermatozoa during capacitation. Biol Reprod 2003;68:1291-8.
  5. Sharma R, Pasqualotto F, Nelson D, Thomas AJ, Agarwal A. The reactive oxygen species-total antioxidant capacity score is a new mea- sure of oxidative stress to predict male infertility. Hum Reprod 1999; 14:2801-7.
  6. Sikka S. Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl 2004;25:5-18.
  7. Fisher H, Aitken R. Comparative analysis of the ability of precursor germ cells and epididymal spermatozoa to generate reactive oxygen metabolites. J Exp Zool 1997;277:390 -400.
  8. Gil-Guzman E, Ollero M, Lopez M, Sharma R, Alvarez J, Thomas AJ, et al. Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum Reprod 2001;16:1922-30.
  9. Ollero M, Gil-Guzman E, Lopez M, Sharma R, Agarwal A, Larson K, et al. Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Hum Reprod 2001;16:1912-21.
  10. Aitken J, Krausz C, Buckingham D. Relationships between biochemical markers for residual sperm cytoplasm, reactive oxygen species gener- ation, and the presence of leukocytes and precursor germ cells in human sperm suspensions. Mol Reprod Dev 1994;39:268 -79.
  11. Huszar G, Vigue L. Correlation between the rate of lipid peroxidation and cellular maturity as measured by creatine kinase activity in human spermatozoa. J Androl 1994;15:71-7.
  12. Gomez E, Buckingham D, Brindle J, Lanzafame F, Irvine D, Aitken R. Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochem- ical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl 1996;17:276 -87.
  13. Twigg J, Fulton N, Gomez E, Irvine D, Aitken R. Analysis of the impact of intracellular reactive oxygen species generation on the struc- tural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod 1998;13:1429 -36.
  14. Aitken R, Fisher H, Fulton N, Gomez E, Knox W, Lewis B, et al. Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine. Mol Reprod Dev 1997;47:468 -82.
  15. Alvarez J, Touchstone J, Blasco L, Storey B. Spontaneous lipid per- oxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J Androl 1987;8:338 -48.
  16. Aitken R, Ryan A, Curry B, Baker M. Multiple forms of redox activity in populations of human spermatozoa. Mol Hum Reprod 2003;9:645-61.
  17. Vernet P, Fulton N, Wallace C, Aitken R. Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa. Biol Reprod 2001;65:1102-13.
  18. Lewis B, Aitken R. A redox-regulated tyrosine phosphorylation cas- cade in rat spermatozoa. J Androl 2001;22:611-22.
  19. Aitken R, Gordon E, Harkiss D, Twigg J, Milne P, Jennings Z, et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 1998;59:1037-46.
  20. Twigg J, Irvine D, Aitken J. Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplas- mic sperm injection. Hum Reprod 1998;13:1864 -71.
  21. Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod 2000;15:1338 -44.
  22. Kemal Duru N, Morshedi M, Oehninger S. Effects of hydrogen perox- ide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril 2000;74:1200 -7.
  23. Agarwal A, Said T. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update 2003;9:331-45.
  24. Fuentes-Mascorro G, Serrano H, Rosado A. Sperm chromatin. Arch Androl 2000;45:215-25.
  25. Saleh R, Agarwal A. Oxidative stress and male infertility: from re- search bench to clinical practice. J Androl 2002;23:737-52.
  26. Teebor G, Boorstein R, Cadet J. The repairability of oxidative free radical mediated damage to DNA: a review. Int J Radiat Biol 1988;54: 131-50.
  27. Shen H, Chia S, Ong C. Evaluation of oxidative DNA damage in human sperm and its association with male infertility. J Androl 1999;20:718 -23.
  28. Zini A, Fischer M, Sharir S, Shayegan B, Phang D, Jarvi K. Prevalence of abnormal sperm DNA denaturation in fertile and infertile men. Urology 2002;60:1069 -72.
  29. Sun J, Jurisicova A, Casper R. Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod 1997;56:602-7.
  30. Tomsu M, Sharma V, Miller D. Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. Hum Reprod 2002;17:1856 -62.
  31. Duran E, Morshedi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod 2002;17:3122-8.
  32. Larson-Cook K, Brannian J, Hansen K, Kasperson K, Aamold E, Evenson DP. Relationship between the outcomes of assisted reproduc- tive techniques and sperm DNA fragmentation as measured by the sperm chromatin structure assay. Fertil Steril 2003;80:895-902.
  33. Zini A, Bielecki R, Phang D, Zenzes M. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril 2001;75: 674 -7.
  34. Tomlinson M, Moffatt O, Manicardi G, Bizzaro D, Afnan M, Sakkas D. Interrelationships between seminal parameters and sperm nuclear DNA damage before and after density gradient centrifugation: implications for assisted conception. Hum Reprod 2001;16:2160 -5.
  35. Erenpreiss J, Hlevicka S, Zalkalns J, Erenpreisa J. Effect of leukocy- tospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl 2002;23:717-23.
  36. World Health Organization. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. New York: Cambridge University Press, 1999.
  37. Endtz A. A rapid staining method for differentiating granulocytes from "germinal cells" in Papanicolaou-stained semen. Acta Cytol 1974;18:2-7.
  38. Gorczyca W, Gong J, Darzynkiewicz Z. Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynu- cleotidyl transferase and nick translation assays. Cancer Res 1993;53: 1945-51.
  39. Hall J, Fishel S, Timson J, Dowell K, Klentzeris L. Human sperm morphology evaluation pre-and post-Percoll gradient centrifugation. Hum Reprod 1995;10:342-6.
  40. Ollero M, Powers R, Alvarez J. Variation of docosahexaenoic acid content in subsets of human spermatozoa at different stages of matu- ration: implications for sperm lipoperoxidative damage. Mol Reprod Dev 2000;55:326 -34.
  41. Armstrong J, Bivalacqua T, Chamulitrat W, Sikka S, Hellstrom W. A comparison of the NADPH oxidase in human sperm and white blood cells. Int J Androl 2002;25:223-9.
  42. de Lamirande E, Harakat A, Gagnon C. Human sperm capacitation induced by biological fluids and progesterone, but not by NADH or NADPH, is associated with the production of superoxide anion. J Androl 1998;19:215-25.
  43. Richer S, Ford W. A critical investigation of NADPH oxidase activity in human spermatozoa. Mol Hum Reprod 2001;7:237-44.
  44. Chen H, Cheung M, Chow P, Cheung A, Liu W, OW. Protection of sperm DNA against oxidative stress in vivo by accessory sex gland secretions in male hamsters. Reproduction 2002;124:491-9.
  45. Potts R, Jefferies T, Notarianni L. Antioxidant capacity of the epidid- ymis. Hum Reprod 1999;14:2513-6.
  46. Potts R, Notarianni L, Jefferies T. Extra-epididymal spermatozoa ex- press nuclear abnormalities. Int J Androl 1999;22:282-8.

Cited by

Sorted by citations

Authors
Said, T. M., Agarwal, A., Sharma, R. K., Thomas, A. J., & Sikka, S. C.
Affiliations
  • Cleveland Clinic (US)
  • Tulane University (US)
Corresponding author
Agarwal, Ashok
Venue
Fertility and Sterility
Publisher
Elsevier BV
Published
2005-01
Volume
83
Issue
1
Pages
95-103
ISSN
0015-0282 (ISSN-L)
OpenAlex
W2125390422
Cited by
189
References
0
Citations by year
2026: 5 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 15 · 2019: 5 · 2018: 3 · 2017: 9 · 2016: 6 · 2015: 11 · 2014: 11 · 2013: 14 · 2012: 19
FWCI
8.69
Type
journal article
Language
en
Open access
Locations
  • Fertility and Sterility (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Reproductive biology and impacts on aquatic species
Keywords
sperm morphology, sperm DNA damage, NADPH, oxidative stress, reactive oxygen species, male infertility, teratozoospermia, sperm DNA fragmentation, chemiluminescence, TUNEL
MeSH terms
DNA Damage, Humans, Male, NADP, Prospective Studies, Spermatozoa, Oxidative Stress

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review