Cited by 259Sperm and Testicular FunctionUrologic and reproductive health conditionsMale Reproductive Health Studies

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Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa

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Saleh, Ramadan A, Agarwal, Ashok, Kandirali, Engin, Sharma, Rakesh K, Thomas, Anthony J, Nada, Essam A, Evenson, Donald P, Alvarez, Juan G·2002·Fertility and Sterility

DOI 10.1016/s0015-0282(02)04237-1

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Abstract

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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Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques
EVENSON, D. P., LARSON, K. L., & JOST, L. K. (2002) · Journal of Andrology · doi:10.1002/j.1939-4640.2002.tb02599.x · Cited by 1,072
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Research works printed but not linked: 35

El Demiry, 1987, Immunocompetent cells in human testis in health and disease, Fertil Steril, 48, 470, 10.1016/S0015-0282(16)59421-7 · DOI
Tomlinson, 1992, The removal of morphologically abnormal sperm forms by phagocytes, Hum Reprod, 7, 517, 10.1093/oxfordjournals.humrep.a137682 · DOI
Thomas, 1997, Increased polymorphonuclear granulocytes in seminal plasma in relation to sperm morphology, Hum Reprod, 12, 2418, 10.1093/humrep/12.11.2418 · DOI
Wolff, 1995, The biologic significance of white blood cells in semen, Fertil Steril, 63, 1143, 10.1016/S0015-0282(16)57588-8 · DOI
Eggert-Kruse, 1992, Differentiation of round cells in semen by means of monoclonal antibodies and relationship with male infertility, Fertil Steril, 58, 1046, 10.1016/S0015-0282(16)55458-2 · DOI
Tomlinson, 1993, Prospective study of leukocytes and leukocyte sub-populations in semen suggests that they are not a cause of male infertility, Fertil Steril, 60, 1069, 10.1016/S0015-0282(16)56412-7 · DOI
Aitken, 1994, Leukocytic infiltration into the human ejaculate and its association with semen quality, oxidative stress and sperm function, J Androl, 15, 343, 10.1002/j.1939-4640.1994.tb00462.x · DOI
Aitken, 1995, Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma, Hum Reprod, 10, 2061, 10.1093/oxfordjournals.humrep.a136237 · DOI
Aitken, 1992, Differential contribution of leukocytes and spermatozoa to the high levels of reactive oxygen species recorded in the ejaculates of oligozoospermic samples, J Reprod Fertil, 97, 441, 10.1530/jrf.0.0970441 · DOI
Krausz, 1994, Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides, Fertil Steril, 62, 599, 10.1016/S0015-0282(16)56952-0 · DOI
Gil-Guzman, 2001, Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation, Hum Reprod, 16, 1922, 10.1093/humrep/16.9.1922 · DOI · Paper page
Ollero, 2001, Characterization of subsets of human spermatozoa at different stages of maturation, Hum Reprod, 16, 1912, 10.1093/humrep/16.9.1912 · DOI · Paper page
Fisher, 1997, Comparative analysis of the ability of precursor germ cells and epididymal spermatozoa to generate reactive oxygen metabolites, J Exp Zool, 277, 390, 10.1002/(SICI)1097-010X(19970401)277:5<390::AID-JEZ5>3.0.CO;2-K · DOI
Gomez, 1998, Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa, Int J Androl, 21, 81, 10.1046/j.1365-2605.1998.00106.x · DOI
Huszar, 1997, Sperm plasma membrane remodeling during spermiogenic maturation in men, Biol Reprod, 56, 1020, 10.1095/biolreprod56.4.1020 · DOI
Aitken, 1999, The Amoroso lecture. The human spermatozoon—a cell in crisis, J Reprod Fertil, 115, 1, 10.1530/jrf.0.1150001 · DOI
Alvarez, 1995, Differential incorporation of fatty acids into and peroxidative loss of fatty acids from phospholipids of human spermatozoa, Mol Reprod Dev, 42, 334, 10.1002/mrd.1080420311 · DOI
Storey, 1998, Human sperm glutathione reductase activity in situ reveals limitation in the glutathione antioxidant defense system due to supply of NADPH, Mol Reprod Dev, 49, 400, 10.1002/(SICI)1098-2795(199804)49:4<400::AID-MRD7>3.0.CO;2-R · DOI
Iwasaki, 1992, Formation of reactive oxygen species in spermatozoa of infertile patients, Fertil Steril, 57, 409, 10.1016/S0015-0282(16)54855-9 · DOI
Sikka, 1995, Role of oxidative stress and antioxidants in male infertility, J Androl, 16, 464, 10.1002/j.1939-4640.1995.tb00566.x · DOI
Kodama, 1997, Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients, Fertil Steril, 65, 519, 10.1016/S0015-0282(97)00236-7 · DOI
Shekarriz, 1995, Positive myeloperoxidase staining (Endtz test) as an indicator of excessive reactive oxygen species formation in semen, J Assist Reprod Genet, 12, 70, 10.1007/BF02211372 · DOI
Krausz, 1992, Analysis of the interaction between N-formyl-methionyl-leucyl-phenylalanine and human sperm suspensions, Fertil Steril, 57, 1317, 10.1016/S0015-0282(16)55094-8 · DOI
Kobayashi, 2001, Quality control of reactive oxygen species measurement by luminol-dependent chemiluminescence assay, J Androl, 22, 568, 10.1002/j.1939-4640.2001.tb02216.x · DOI
Sharma, 1999, The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility, Hum Reprod, 14, 2801, 10.1093/humrep/14.11.2801 · DOI
Huszar, 2000, Putative creatine kinase M-isoform in human sperm is identified as the 70-kilodalton heat shock protein HspA2, Biol Reprod, 63, 925, 10.1095/biolreprod63.3.925 · DOI
Huszar, 1993, Incomplete development of human spermatozoa is associated with increased creatine phosphokinase concentration and abnormal head morphology, Mol Reprod Dev, 34, 292, 10.1002/mrd.1080340309 · DOI
Sidhu, 1998, Relationship between creatine kinase levels and clinical diagnosis of infertility, J Assist Reprod Genet, 15, 188, 10.1023/A:1023096201880 · DOI
Hallak, 2001, Creatine kinase as an indicator of sperm quality and maturity in men with oligospermia, Urology, 58, 446, 10.1016/S0090-4295(01)01224-9 · DOI
Huszar, 1994, Correlation between the rate of lipid peroxidation and cellular maturity as measured by creatine kinase activity in human spermatozoa, J Androl, 15, 71, 10.1002/j.1939-4640.1994.tb01687.x · DOI
Gomez, 1996, Impact of IVF-ET culture media on peroxidative damage to human spermatozoa, Fertil Steril, 65, 880, 10.1016/S0015-0282(16)58233-8 · DOI
De Lamirande, 1995, Impact of reactive oxygen species on spermatozoa, Hum Reprod, 10, 15, 10.1093/humrep/10.suppl_1.15 · DOI
Armstrong, 1999, Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism, Free Radic Biol Med, 26, 869, 10.1016/S0891-5849(98)00275-5 · DOI
Sun, 1997, Detection of deoxyribonucleic acid fragmentation in human sperm, Biol Reprod, 56, 602, 10.1095/biolreprod56.3.602 · DOI
Kiessling, 1995, Semen leukocytes, Fertil Steril, 60, 196, 10.1016/S0015-0282(16)57681-X · DOI

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Moubasher, A., Sayed, H., Mosaad, E., Mahmoud, A., Farag, F., & Taha, E. (2018) · Central European Journal of Urology · doi:10.5173/ceju.2018.1724 · Cited by 29
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Agarwal, A., Sharma, R., Gupta, S., Harlev, A., Ahmad, G., du Plessis, S., Esteves, S., Wang, S., & Durairajanayagam, D. (2017) · doi:10.1007/978-3-319-48427-3 · Cited by 26
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Korrovits, P., Punab, M., Türk, S., & Mändar, R. (2006) · European Urology · doi:10.1016/j.eururo.2006.05.013 · Cited by 22
“However, according to our previous study results [4] as well as the results of some other studies [5–8], this limit probably needs to be lowered.”
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Ardekani, O. S., Letafati, A., Dehkordi, S. E., Farahani, A. V., Bahari, M., Mahdavi, B., Ariamand, N., Taghvaei, M., Kohkalani, M., Pirkooh, A. A., et al. (2025) · European journal of medical research · doi:10.1186/s40001-025-02605-4 · Cited by 22
“Thus, since Leukocytes are the primary contributors to the generation of ROS in semen, a higher concentration of leukocytes in the semen can lead to increased production of ROS, which negatively impacts sperm functionality [132, 133].”
Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction
Sethuram, R., Bai, D., & Abu‐Soud, H. M. (2021) · Reproductive Sciences · doi:10.1007/s43032-020-00400-6 · Cited by 29
Cytosolic and mitochondrial ROS: which one is associated with poor chromatin remodeling?
Kiani-Esfahani, A., Bahrami, S., Tavalaee, M., Deemeh, M., Mahjour, A. A., & Nasr-Esfahani, M. (2013) · Systems Biology in Reproductive Medicine · doi:10.3109/19396368.2013.829536 · Cited by 24
Use of Diagnostic Testing to Detect Infertility
Hwang, K., Lipshultz, L. I., & Lamb, D. J. (2010) · Current Urology Reports · doi:10.1007/s11934-010-0154-0 · Cited by 27
Oxidative stress and acrosomal morphology: A cause of infertility in patients with normal semen parameters
El-Taieb, M. A., Ali, M. A., & Nada, E. (2015) · Middle East Fertility Society Journal · doi:10.1016/j.mefs.2014.05.003 · Cited by 23
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Ubilla, A., & Valdebenito, I. (2011) · doi:10.4067/s0718-560x2011000200015 · Cited by 23
“Lahnsteiner et al., (2010a) and Lahnsteiner et al., (2010b) incorporated different antioxidants for defense from the ORS´s into a sperm diluent, finding positive effects on sperm viability (sperm motility, membrane integrity and lipid peroxidation) in stored semen of different teleostei fish for 72 to 120 h with uric…”
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The occurrence of reactive oxygen species in the semen of males from infertile couples.
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Oxidative Stress as an Underlying Mechanism of Bacteria-Inflicted Damage to Male Gametes
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Background
Resistin in Human Seminal Plasma: Relationship with Lipid Peroxidation, CAT Activity, GSH/GSSG Ratio, and Semen Parameters
Moretti, E., Micheli, L., Noto, D., Fiaschi, A. I., Menchiari, A., & Cerretani, D. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2192093 · Cited by 22
“It is noteworthy that, in our study, MDA was significantly increased in the leukocytospermia group compared to the varicocele group, indicating that leukocytes, known to be one of the major sources of ROS and to stimulate sperm to produce ROS [45], can induce the oxidative stress.”
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Expression of peroxiredoxins in the human testis, epididymis and spermatozoa and their role in preventing H2O2-induced damage to spermatozoa.
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“They verified, by using single-cell gel electrophoresis (SCGE) and sperm chromatin structure analysis (SCSA), that white blood cells are the main source of ROS production in semen and have a great impact on DNA integrity (56).”
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“There is evidence to suggest that leukocytospermia is associated with a decrease in semen quality (Wolff et al., 1990; Plante et al., 1994; Saleh et al., 2002; Aziz et al., 2004), however, results are inconsistent (Tomlinson et al., 1993; Aitken et al., 1995; Kaleli et al., 2000; Ziyyat et al.,…”
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Seminal plasma stimulates cytokine production in endometrial epithelial cell cultures independently of the presence of leucocytes
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“…et al., 2005) and may explain, at least in part, infertility in men with LCS. Removal of leucocytes from semen samples used for assisted reproduction has been suggested in order to reduce oxidative stress and improve gamete quality (Sharma et al., 2001; Saleh et al., 2002; Sheweita et al., 2005).”
Background
Seminal elastase-inhibitor complex, a marker of genital tract inflammation, and negative IVF outcome measures: role for a silent inflammation?
Zorn, B., Virant-Klun, I., Vidmar, G., Sešek-Briški, A., Kolbezen, M., & Meden-Vrtovec, H. (2004) · International Journal of Andrology · doi:10.1111/j.1365-2605.2004.00500.x · Cited by 17
Significance of oxidative stress and sperm chromatin damage in male infertility.
Agarwal, A., Vriese, S. D., & Christophe, A. (2003) · doi:10.1201/9781439822234.ch13 · Cited by 17
“Levels of ROS production by pure sperm suspensions were found to be significantly higher in infertile men with leukocytospermia than in infertile men without leukocytospermia and were strongly correlated with seminal leukocyte concentration (101) (Table 13.”
BackgroundSelf-citation
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Kratz, E., Kałuża, A., Ferens-Sieczkowska, M., Olejnik, B., Fiutek, R., Zimmer, M., & Piwowar, A. (2016) · Reproduction, Fertility and Development · doi:10.1071/rd14268 · Cited by 16
“High levels of ROS are toxic for spermatozoa; however, in small amounts, they are necessary for sperm fertilising capability, including sperm hyperactivation, capacitation and the acrosomal reaction, as well as their ability to bind to the zona pellucida (Saleh et al. 2002).”
Background
Correlation between leukocytospermia and oxidative stress in male partners of infertile couples with leukocytospermia
Aggarwal, R., Puri, M., Dada, R., & Saurabh, G. (2015) · doi:10.5455/2320-1770.ijrcog20150230 · Cited by 15
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Durairajanayagam, D. (2019) · Oxidants, Antioxidants and Impact of the Oxidative Status in Male Reproduction · doi:10.1016/b978-0-12-812501-4.00008-0 · Cited by 15
The effect of screening and treatment of Ureaplasma urealyticum infection on semen parameters in asymptomatic leukocytospermia: a case–control study
Zhang, Q.-F., Zhang, Y.-J., Wang, S., Wei, Y., Li, F., & Feng, K. (2020) · BMC Urology · doi:10.1186/s12894-020-00742-y · Cited by 14
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Ribas-Maynou, J., García-Peiró, A., Martínez-Heredia, J., Fernández-Encinas, A., Abad, C., Amengual, M., Navarro, J., & Benet, J. (2015) · Andrologia · doi:10.1111/and.12258 · Cited by 13
“Another group of patients that could have increased oxidative stress are patients with leukocytospermia (Saleh et al., 2002), but it has been described that they do not show an increase in the nuclear degraded subpopulation (Rodriguez et al., 2012; Gosalvez et al., 2013).”
Background
Supraphysiological Free Radical Levels and their Pathogenesis in Male Infertility
V, D. (2012) · doi:10.4172/2161-038x.1000114 · Cited by 13
Synthetic Antioxidants
Stokes, P., Belay, R. E., & Ko, E. (2020) · Springer eBooks · doi:10.1007/978-3-030-32300-4_44 · Cited by 7
Chapter 5 Slow Freezing of Human Sperm.
Agarwal, A., & Tvrdá, E. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6828-2_5 · Cited by 12
Self-citation
Oxidative Stress, Sperm DNA Fragmentation, or Both? Optimizing Test Selection in Male Infertility Evaluation
Kaltsas, A., Papaharitou, S., Sengupta, P., Saleh, R., & Agarwal, A. (2026) · Antioxidants · doi:10.3390/antiox15030293 · Cited by 11
“These leukocytes generate high levels of ROS that overwhelm seminal antioxidant defenses, de-press antioxidant capacity, and impair sperm function and DNA integrity, thereby increasing SDF [104,105].”
Self-citation
Role of Leukocytospermia in the Management of Male Infertility: Decoding a Mystery for the Busy Clinicians
Dutta, S., Bocu, K., & Agarwal, A. (2024) · The World Journal of Men's Health · doi:10.5534/wjmh.240152 · Cited by 11
“Leukocytospermia affects 10% to 20% of patients with infertility issues [28] and is linked to reduced fertility [12,29-31].”
Self-citation
Sperm DNA integrity: a special issue exploring the causes, consequences, and treatment of DNA damage in human spermatozoa
Aitken, R. J. (2023) · Andrology · doi:10.1111/andr.13503 · Cited by 11
Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice
Mojidra, B., Archana, K., Gautam, A., Verma, Y., Lakkad, B., & Kumar, S. (2009) · Toxicology and industrial health · doi:10.1177/0748233709345939 · Cited by 11
Sperm DNA Fragmentation is Significantly Increased in Those Men with Morphologically Abnormal Spermatozoa
García-Ferreyra, J. (2014) · Journal of Fertilization In Vitro - IVF-Worldwide Reproductive Medicine Genetics & Stem Cell Biology · doi:10.4172/2375-4508.1000131 · Cited by 9
Genetic variations of antioxidant genes and their association with male infertility in Vietnamese men
Bach, H. A., Vu, P. N., Ma, T. H. T., Hà, N. H., Duc, P. T., Minh, D. B., Nong, V. H., & Tôn, N. Đ. (2023) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24829 · Cited by 11
Light and electron microscopic study of the effect of L-carnitine on the sperm morphology among sub fertile men
El-baset, S. A. A., El-Wahab, S. M. A., Mansour, A., & Mohamed, E. A. H. (2010) · doi:10.1016/j.mefs.2010.04.005 · Cited by 9
Reactive oxygen species and their influence on stallion semen fertility - a review
Pagl, R., Aurich, J., & Aurich, C. (2006) · Pferdeheilkunde Equine Medicine · doi:10.21836/pem20060217 · Cited by 9
The Clinical Management of Leukocytospermia in Male Infertility: A Narrative Review
Hussain, U., Venishetty, N., Alkassis, M., & Raheem, O. A. (2024) · Uro · doi:10.3390/uro4020004 · Cited by 8
“Studies comparing pure sperm samples from patients with leukocytospermia and patients without saw a significantly higher level of ROS production from the sample of the patients with leukocytospermia [22].”
BackgroundInfluential
[Infections and male infertility].
Saint, F., Huyghe, E., Methorst, C., Priam, A., de Mazancourt, E. D., Bruyère, F., & Faix, A. (2023) · Progrès en urologie (Paris) · doi:10.1016/j.purol.2023.09.015 · Cited by 8
Human MOSPD2: A bacterial Lmb mimicked auto-antigen is involved in immune infertility
Parida, R. (2019) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2019.100002 · Cited by 8
Reduced Seminal Concentration of CD45pos Cells after Follicle-Stimulating Hormone Treatment in Selected Patients with Idiopathic Oligoasthenoteratozoospermia
Condorelli, R., Calogero, A., Vicari, E., Mongioì, L., Burgio, G., Cannarella, R., Giacone, F., Iacoviello, L., Morgia, G., Favilla, V., et al. (2014) · International Journal of Endocrinology · doi:10.1155/2014/372060 · Cited by 8
Effects of apple and orange juices on quality of refrigerated goat semen
Adekunle, O., Daramola, O., Sowande, S. O., Abiona, A. J., & Abioja, O. M. (2018) · doi:10.2298/jas1801053a · Cited by 8
“Sperm cells generally have antioxidants as a defense mechanism against the attack of reactive oxygen species, however, this defense system is inadequate (Saleh et al., 2002).”
Background
Free Radicals in Andrology
Agarwal, A. K., & Majzoub, A. A. (2016) · Trends in andrology and sexual medicine · doi:10.1007/978-3-319-41749-3_1 · Cited by 6
Self-citation
Clinical Consequences of Oxidative Stress in Male Infertility
Said, T., Gokul, S., & Agarwal, A. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-776-7_24 · Cited by 8
Self-citation
Molecular Mechanisms of Antioxidants in Male Infertility
Hwang, K., & Lamb, D. (2012) · doi:10.1007/978-1-4614-3335-4_5 · Cited by 8
Oxidative Stress, DNA Damage, and Apoptosis in Male Infertility
Said, T., Fischer-Hammadeh, C., Hamad, M., Refaat, K. M., & Hammadeh, M. (2012) · doi:10.1007/978-1-61779-776-7_20 · Cited by 8
Association of oxidative balance score with incident cardiovascular disease in patients with type 2 diabetes: findings of the UK Biobank study
Cheng, L., Wang, X., Dang, K., Hu, J., Zhang, J., Xu, X., Pan, S., Qi, X., & Li, Y. (2025) · European Journal of Nutrition · doi:10.1007/s00394-024-03552-2 · Cited by 7
An Alternative Application of Magnetic-Activated Cell Sorting: CD45 and CD235a Based Purification of Semen and Testicular Tissue Samples
Czétány, P., Balló, A., Márk, L., Török, A., Szántó, Á., & Máté, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073627 · Cited by 7
Effect of macrophages in semen on sperm quality
Chen, G., & Zheng, B. (2021) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-021-00724-1 · Cited by 9
Production of ROS and its effects on mitochondrial and nuclear DNA, human spermatozoa, and sperm function
Darmawan, H. (2007) · doi:10.13181/mji.v16i2.268 · Cited by 7
Reliable Detection of Excessive Sperm Ros Production in Subfertile Patients: How Many Men with Oxidative Stress?
Calamai, C., Chelli, E., Ammar, O., Tanturli, M., Vignozzi, L., & Muratori, M. (2024) · Antioxidants · doi:10.3390/antiox13091123 · Cited by 6
“Beside assessing the main sperm parameters, routine semen analysis detects several semen traits that have been associated to oxidative stress, like viscosity [49–51], leuko-cytospermia [52,53] and bacteriospermia [54].”
Myeloperoxidase and lactoferrin expression in semen fluid: Novel markers of male infertility risk?
Omes, C., Amici, M. D., Tomasoni, V., Todaro, F., Torre, C., & Nappi, R. (2020) · Immunobiology · doi:10.1016/j.imbio.2020.151999 · Cited by 6
Fragmentación del ADN espermático
Berenguer, J., Peregrín, P. C., López-Fernández, C., Fernández, J., & Calonge, R. N. (2008) · doi:10.1016/s1698-031x(08)76145-4 · Cited by 6
INFORMATIVENESS OF COMBINED HUMAN SEMEN ANALYSIS ON THE WAY TO CLARIFY THE CAUSES OF REPRODUCTIVE DYSFUNCTION: BASIC SEMEN EXAMINATION AND SPERM SEDIMENT CYTOLOGY (SSC)
Sapozhkova, Z. (2023) · Laboratornaya i klinicheskaya meditsina Farmatsiya · doi:10.14489/lcmp.2023.01.pp.019-036 · Cited by 6
Infertility in the Male: Determination of seminal oxidants (reactive oxygen species)
Agarwal, A., & Deepinder, F. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511635656.040 · Cited by 6
Self-citation
Research progress on the multidimensional mechanisms underlying impaired spermatogenesis induced by pathological microenvironment remodeling in chronic prostatitis
Li, J., Jiang, Z.-P., Luo, W., Tang, K.-H., Liang, D.-C., Luo, X.-J., Liu, L., Long, Z.-M., Huang, H.-M., Chen, W.-W., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1793156 · Cited by 5
“Mechanistic studies provide molecular explanations: bacterial products can stimulate leukocytes to undergo a respiratory burst, releasing massive amounts of ROS (187, 194).”
Prostatitis-Related Male Infertility: From Inflammation and Dysbiosis to Sperm DNA Damage
Kaltsas, A., Pantazis, N., Tzikoulis, V., Roidos, C., Palapela, N., Tsiampali, C., Symeonidis, E., Zachariou, A., Sofikitis, N., & Dimitriadis, F. (2026) · Diagnostics · doi:10.3390/diagnostics16050722 · Cited by 5
“By reducing prostatic pain and swelling, these agents can secondarily improve ejaculatory function and semen parameters (motility, viscosity) that are impaired by inflammation [99,100].”
The sperm chromatin structure assay does not detect alterations in sperm chromatin structure induced by hydrogen peroxide
Bittner-Schwerda, L., Malama, E., Siuda, M., van Loon, B., & Bollwein, H. (2022) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2022.107094 · Cited by 8
Auricularia polytricha restores altered reproductive parameters in streptozotocin-induced diabetic Wistar rat
Agbor, C., Anyanwu, G., & Audu, S. (2020) · Journal of Basic and Applied Zoology · doi:10.1186/s41936-020-00165-z · Cited by 5
SPERM CHROMATIN DISPERSION TEST FOR EXAMINATION OF INFERTILE MALE: FROM СLINICAL TRIALS OF FIRST RUSSIAN KIT GEMSTANDART–HALOSPERM L&Q
Sapozhkova, Z., Eremin, K., & Patsap, O. (2022) · Laboratornaya i klinicheskaya meditsina Farmatsiya · doi:10.14489/lcmp.2022.03.pp.037-056 · Cited by 5
Vitamin B12 and Reproductive Health: Clinical Insights, Emerging Mechanistic Understanding, and Nutritional Aspects
Mathew, A. R., Selita, E., Regano, C., Bianco, C., Corsetti, V., Cavallucci, V., Moreno, S., Tata, A., & Fidaleo, M. (2026) · Molecular Reproduction and Development · doi:10.1002/mrd.70088 · Cited by 4
“…for motility, capacitation, and acrosome responsiveness—OS is an established driver of impaired function and DNA damage, providing a plausible route from VitB12 insufficiency (often accompanied by elevated homocysteine) to reduced fertilizing capacity (Kralikova et al. 2017; Saleh et al. 2002).”
Cell‐type‐specific determination of reactive oxygen species by flow cytometry
Hajnal, Á., Bogdándi, N., Marokházi, J., Guba, D., & Mikus, E. (2023) · Andrology · doi:10.1111/andr.13473 · Cited by 4
“23,24 Despite The determined cut-off value displayed high specificity and selectivity.”
Background
Dietary omega‐3 polyunsaturated fatty acids induce plasminogen activator activity and DNA damage in rabbit spermatozoa
Kokoli, A., Lavrentiadou, S., Zervos, I., Tsantarliotou, M., Georgiadis, M., Nikolaidis, E., Botsoglou, N., Boscos, C., & Taitzoglou, I. (2017) · Andrologia · doi:10.1111/and.12776 · Cited by 4
“, 2001) or extracellularly by neutrophils and/or other leucocytes (Baumber, Vo, Sabeur, & Ball, 2002; Saleh et al., 2002), may overwhelm or even surpass the antioxidant defenses of the semen plasma, and thus lead to oxidative stress.”
Background
ORIGINAL ARTICLE: The Effect of Oxidative Environment on Immunosuppressive Properties of Human Seminal Plasma
Badia, R., Iborra, A., Palacio, J., Antich, M., & Martínez, P. (2008) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2008.00634.x · Cited by 4
Correlation Between Oxidative Stress Generation, Reticular Fiber Density and Testicular Histomorphometric Parameters Of Streptozotocin-Induced Diabetic Wistar Rat
Anyanwu, G., & Agbor, C. (2021) · Journal of Bio-Science · doi:10.3329/jbs.v29i2.54949 · Cited by 4
“…is required for sperm cells to acquire fertilization potentials necessary for the process of capacitation, acrosome reaction and possibly fusion (Saleh et al. 2002), but excessive generation of ROS as in hyperglycaemic condition, without a corresponding balance in antioxidant production…”
Background
Leukocytes as a Cause of Oxidative Stress
Henkel, R., & Solomon, M. C. (2019) · Oxidants, Antioxidants and Impact of the Oxidative Status in Male Reproduction · doi:10.1016/b978-0-12-812501-4.00005-5 · Cited by 4
Seminal Malondialdehyde Concentration And Superoxide Dismutase , Catalase Activity In Male Infertility 3 of 7
(2018) · doi:10.5580/243d · Cited by 4
Antioxidants and Other Potent Strategies to Reduce Oxidative Stress in Semen
Bansal, A. (2015) · doi:10.1007/978-81-322-2035-0_24 · Cited by 4
Molecular Advances in Male Infertility and Fertility: Importance of Redox Regulation and Oxidative Stress
Aitken, R. J., Vazquez-Levin, M. H., Hallak, J. S., Teixeira, T. A., & Hallak, J. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093819 · Cited by 4
The Effects of Alkaloids Fraction of Cyperus esculentus on Some Biochemical Parameters and Histopathology of the Testis of Lead-Induced Toxicity
Anyanwu, G., Hassan, L., Abireh, I., & Nto, N. (2021) · Journal of Pharmaceutical Research International · doi:10.9734/jpri/2021/v33i50a33382 · Cited by 3
“radicals such as OH and H2O2 in the testis of the lead-exposed rat [26,29].”
Background
Effect of Centrifugation on Motility, Sperm Capacitation and Acrosome Reaction in Soy Bean and Avocado Seed Milk Extenders of Cryopreserved Goat Spermatozoa
Daramola, J. (2017) · doi:10.1515/ats-2017-0002 · Cited by 3
Comparación entre el test de fragmentación de ADN espermático mediante la técnica de SCD y el índice de vitalidad medida con el test de naranja de acridina
López, L. O., Vila, E. O., Domínguez, P. L., Segovia, A. G., Gomez, I. O., Calonge, R. N., & Peregrín, P. C. (2010) · doi:10.1016/s1698-031x(10)70022-4 · Cited by 3
[Medical treatments and hygiene and dietary measures].
Fauque, P. (2007) · Journal de gynecologie, obstetrique et biologie de la reproduction · doi:10.1016/s0368-2315(07)78735-5 · Cited by 3
Leukocytospermia and Oxidative Stress
Flint, M., Agarwal, A., & du Plessis, S. (2012) · doi:10.1007/978-1-61779-776-7_23 · Cited by 3
Self-citation
Reactive Oxygen and Nitrogen Species in Male Reproductive Health: From Molecular Mechanisms to Clinical Consequences
Wang, S., Chung, J. P., & Chan, D. Y. L. (2026) · Antioxidants · doi:10.3390/antiox15070795 · Cited by 2
“In this healthy, homeostatic state, leukocyte-derived ROS production remains low and strictly regulated [55].”
Deciphering dose and time dependent effect of supplementing SNP and L-NAME in extender on progressive motility of Murrah bull spermatozoa
Upadhyay, V., Roy, A. K., Pandita, S., Kshetrimayum, D., Patoliya, P., Raval, K., Dewry, R., Sarita, S., & Nath, S. (2021) · Indian Journal of Animal Sciences · doi:10.56093/ijans.v91i11.118126 · Cited by 2
Effects of Different Antioxidants on Sperm Parameters in Infertile Males
Samra, M. (2018) · Journal of Medical Science And clinical Research · doi:10.18535/jmscr/v6i2.117 · Cited by 2
Compendium of Oxidative Stress-Related Research from Cleveland Clinic (1993–2016)
Durairajanayagam, D., Dhillon, A. S., Salasin, R., Kashou, A. H., & Kothandaraman, N. (2017) · Springer eBooks · doi:10.1007/978-3-319-48427-3_8 · Cited by 2
New Developments for the Enhancement of Male Reproductive Health Using Antioxidant Therapy: A Critical Review of the Literature
Tremellen, K. (2020) · Springer eBooks · doi:10.1007/978-3-030-32300-4_45 · Cited by 2
Role of Assisted Reproduction Techniques in the Management of Unexplained Male Infertility
Gangrade, B. K., Patel, Z. P., & Patel, S. (2015) · doi:10.1007/978-1-4939-2140-9_31 · Cited by 2
Impact of Paternal Exposure to Gonadotoxins on Embryo and Offspring and the Male Evaluation
Hwang, K., Gittens, P. R., Avila, D., & Lipshultz, L. I. (2011) · Springer eBooks · doi:10.1007/978-1-4419-1783-6_21 · Cited by 1
“Excessive ROS in the ejaculate correlates with increasing sperm DNA damage [88, 97, 118].”
BackgroundMethod
Epididymal antimicrobial peptides: the role in sperm function (review)
Шабанов, П. А., Шамова, О. В., Орлов, Д. С., Грязнов, А. Ю., & Янчук, Н. О. (2021) · Nauchno-prakticheskii zhurnal «Patogenez» · doi:10.25557/2310-0435.2021.01.4-12 · Cited by 1
“ловых клетках, изменением активности поверхностных белков, транскрипционных факторов клеток иммунной защиты и чрезмерной продукцией цитокинов, среди которых одна из ведущих ролей в запуске процесса апоптоза сперматозоидов принадлежит фактору некроза опухоли альфа (ФНО-α) [34-36].”
Pathological Effects of Elevated Reactive Oxygen Species on Sperm Function
Ahmad, G., & Agarwal, A. (2016) · CRC Press eBooks · doi:10.1201/b20228-38 · Cited by 1
Self-citation
Evaluation of the impact of leucocytospermia on semen oxidative status by chemiluminescence technique in infertile men
Sellami, A., Chakroun, N., Rtaib, Y., Hdhili, H., Mansour, R. B., Dolira, L., Chaabène, K., Keskes, L., Lassoued, S., & Rebai, T. (2013) · doi:10.4236/abb.2013.411a2005 · Cited by 1
An Introduction to Male Reproductive Medicine: Male reproductive immunology
Brannigan, R. (2011) · doi:10.1017/cbo9780511736254.006 · Cited by 1
Composition lipidique des spermatozoides humains et susceptibilité au stress oxydant avant et après migration dans le mucus cervical
Feki, N. C., Thérond, P., Jouannet, P., & Auger, J. (2003) · doi:10.1007/bf03035205 · Cited by 1
“Dans une Etude rEcente, Saleh et al. [ 64 ] ont suggErE que les PNN stimulent ou induisent la production de quantitEs ElevEes de DAO par les spermatozoi"des eux mOmes : les spermatozoYdes des hommes infertiles ayant une leucospermie avaient un niveau de production spontanEe et induite de DAO par le PMA significativeme…”
Background
Seminal Oxidation-Reduction Potential
Rana, M., & Agarwal, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-32300-4_30 · Cited by 1
Self-citation
Beyond Leukocyte-Rich Versus Leukocyte-Poor PRP: A Precision Framework for Male Infertility
Petrović, D., Pantovic, V., Dinic, M., Švraka, D., Vujović, S., Vukotić, M., & Ljubić, A. (2026) · Reproductive Medicine · doi:10.3390/reprodmed7040064
Association Between Leukocytospermia and Varicocele in Patients With Infertility
Eldamnhoury, E. M., & El-Sakka, A. (2026) · American Journal of Reproductive Immunology · doi:10.1111/aji.70308

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
ORCID: Saleh, Ramadan A
Agarwal, Ashok
Sharma, Rakesh K
Nada, Essam A
Evenson, Donald P
Venue: Fertility and Sterility
Publisher: Elsevier BV
Published: 2002-12
Volume: 78
Issue: 6
Pages: 1215-1224
ISSN: 0015-0282 (ISSN-L)
DOI: 10.1016/s0015-0282(02)04237-1
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 7117 d)
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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Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa

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