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Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa
Open accessAbstract
To investigate the role of increased seminal leukocytes in enhancing reactive oxygen species (ROS) production by human spermatozoa.A prospective study. Male infertility clinic.Forty-eight infertile men. Standard semen analysis. Assessment of sperm nuclear DNA damage by sperm chromatin structure assay. Incubation of spermatozoa from nonleukocytospermic samples with blood neutrophils. Spontaneous and phorbol 12-myristate 13-acetate (PMA)-induced ROS production in pure-sperm suspensions (after removal of leukocytes) as measured by a chemiluminescence assay. Levels of spontaneous and PMA-induced ROS production in pure-sperm suspensions from the infertile men with a diagnosis of leukocytospermia (n = 16) were significantly higher compared with the case of infertile men without leukocytospermia (n = 32) and with the case of a control group of healthy volunteers (n = 13). A similar pattern of increased ROS was observed when spermatozoa were incubated with blood neutrophils. Leukocytospermia was associated with a significant decrease in sperm motility and increase in DNA damage. Increased seminal leukocytes may play a role in stimulating ROS production by human spermatozoa. Such stimulation may be mediated via direct cell-cell contact or by soluble products released by leukocytes. Poor sperm quality in leukocytospermic samples may be due to leukocyte-mediated oxidative stress.
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“Due to the production of excessive amounts of ROS in numerous medical conditions, including varicocele [43], leukocytospermia [44], diabetes mellitus [45], and obesity [46], seminal OS develops.”
From The Sixth Edition of the WHO Manual for Human Semen Analysis: A Critical Review and SWOT Analysis (2021) · cites this paper as [44]
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Cited by
Sorted by citations
Role of reactive oxygen species in the pathophysiology of human reproduction.
Agarwal, A., Saleh, R., & Bedaiwy, M. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04948-8 · Cited by 1,578
“by pure sperm suspensions from infertile men with a laboratory diagnosis of leukocytospermia were significantly higher than were those from infertile men without leukocytospermia (Table 1) (59).”
ResultSelf-citationOxidative stress and male infertility—a clinical perspective
Tremellen, K. P. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn004 · Cited by 1,544
“Smoking results in a 48% increase in seminal leukocyte concentrations and a 107% increase in seminal ROS levels (Saleh et al., 2002a).”
BackgroundMethodOxidative stress and male infertility
Bisht, S., Faiq, M. A., Tolahunase, M., & Dada, R. (2017) · Nature Reviews Urology · doi:10.1038/nrurol.2017.69 · Cited by 918
Impacts of Oxidative Stress and Antioxidants on Semen Functions
Bansal, A. K., & Bilaspuri, G. S. (2010) · Veterinary Medicine International · doi:10.4061/2011/686137 · Cited by 802
“Leukocytes particularly neutrophils and macrophages have been associated with excessive ROS production and they ultimately cause sperm dysfunction [21, 34–40].”
BackgroundRole of antioxidants in treatment of male infertility: an overview of the literature.
Agarwal, A., Nallella, K. P., Allamaneni, S., & Said, T. (2004) · Reproductive Biomedicine Online · doi:10.1016/s1472-6483(10)61641-0 · Cited by 538
“Initially, clinicians should identify and treat the cause for increased ROS production, for example reproductive tract infections, smoking, and varicocoele (Hendin et al., 1999; Kolettis et al., 1999; Pasqualotto et al., 2000b; Sharma et al., 2001; Saleh et al., 2002c).”
BackgroundSelf-citation
Metadata
- Authors
- Saleh, R. A., Agarwal, A., Kandirali, E., Sharma, R. K., Thomas, A. J., Nada, E. A., Evenson, D. P., & Alvarez, J. G.
- Affiliations
- Cleveland Clinic (US)
- South Valley University (EG)
- South Dakota State University (US)
- Corresponding author
- Agarwal, Ashok
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 78
- Issue
- 6
- Pages
- 1215-1224
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2129317574
- Cited by
- 259
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 13 · 2020: 11 · 2019: 5 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 13 · 2014: 21 · 2013: 11 · 2012: 16
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cleveland Clinic Foundation
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Urology › Urologic and reproductive health conditions
- Health Sciences › Medicine › Urology › Male Reproductive Health Studies
- Keywords
- leukocytospermia, reactive oxygen species, spermatozoa, seminal leukocytes, neutrophils, oxidative stress, male infertility, sperm DNA damage, sperm motility, phorbol myristate acetate
- MeSH terms
- DNA Damage, Humans, Infertility, Male, Leukocytes, Male, Neutrophils, Prospective Studies, Reference Values, Sperm Motility, Spermatozoa, Tetradecanoylphorbol Acetate, Reactive Oxygen Species
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