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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Causes and consequences of oxidative stress in spermatozoa

Robert John Aitken A D , Zamira Gibb A , Mark A. Baker A , Joel Drevet B and Parviz Gharagozloo C
+ Author Affiliations
- Author Affiliations

A Priority Research Centre in Reproductive Science and Hunter Medical Research Institute, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia.

B GReD laboratory, CNRS UMR6293-INSERM U1103-Clermont Université, 63171 BP80006, Aubière cedex, France.

C CellOxess LLC, 15 Roszel Street, Princeton, NJ 08540, USA.

D Corresponding author. Email: john.aitken@newcastle.edu.au

Reproduction, Fertility and Development 28(2) 1-10 https://doi.org/10.1071/RD15325
Published: 3 December 2015

Abstract

Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent.

Additional keywords: apoptosis, fertilizing potential, lipid peroxidation, male germ line, oxidative DNA damage, ROS generation.


References

Aitken, R. J. (1999). The Amoroso Lecture. The human spermatozoon: a cell in crisis? J. Reprod. Fertil. 115, 1–7.
The Amoroso Lecture. The human spermatozoon: a cell in crisis?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXhs12isro%3D&md5=c39906b4f086b5567855be3775a9e3b6CAS | 10341716PubMed |

Aitken, R. J. (2006). Sperm function tests and fertility. Int. J. Androl. 29, 69–75.
Sperm function tests and fertility.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD28%2FotV2juw%3D%3D&md5=bb3a3a00d57a40b22ecc0a2d6e4fd186CAS | 16466526PubMed |

Aitken, R. J. (2014). Age, the environment and our reproductive future: bonking baby boomers and the future of sex. Reproduction 147, S1–S11.
Age, the environment and our reproductive future: bonking baby boomers and the future of sex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXisFartrw%3D&md5=335ba1934061e8697962cea851b2cb07CAS | 24194569PubMed |

Aitken, R. J., and Clarkson, J. S. (1987). Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J. Reprod. Fertil. 81, 459–469.
Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXltlyjsw%3D%3D&md5=2801cada0abf6be4e5b3a123428019b5CAS | 2828610PubMed |

Aitken, R. J., and Curry, B. J. (2011). Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid. Redox Signal. 14, 367–381.
Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SjsA%3D%3D&md5=9fc3d78a21b9a670aada29a805404d0aCAS | 20522002PubMed |

Aitken, R. J., and Nixon, B. (2013). Sperm capacitation: a distant landscape glimpsed but unexplored. Mol. Hum. Reprod. 19, 785–793.
Sperm capacitation: a distant landscape glimpsed but unexplored.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvVOgurfM&md5=610a7a91f3d477aba29653e46803450dCAS | 24071444PubMed |

Aitken, R. J., Thatcher, S., Glasier, A. F., Clarkson, J. S., Wu, F. C., and Baird, D. T. (1987). Relative ability of modified versions of the hamster oocyte penetration test, incorporating hyperosmotic medium or the ionophore A23187, to predict IVF outcome. Hum. Reprod. 2, 227–231.
| 1:STN:280:DyaL2s3ltFartA%3D%3D&md5=7da1c3b24c9334f99b60c257b08f8b74CAS | 3110205PubMed |

Aitken, R. J., Clarkson, J. S., and Fishel, S. (1989). Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol. Reprod. 41, 183–197.
Generation of reactive oxygen species, lipid peroxidation, and human sperm function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXlslWksLs%3D&md5=c2630bf37e42c6fc8ea244e7c0b7c49fCAS | 2553141PubMed |

Aitken, R. J., Irvine, D. S., and Wu, F. C. (1991). Prospective analysis of sperm–oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am. J. Obstet. Gynecol. 164, 542–551.
Prospective analysis of sperm–oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M7islGntg%3D%3D&md5=402531a6a0a99eef944540eec26c77b5CAS | 1992700PubMed |

Aitken, R. J., Buckingham, D., West, K., Wu, F. C., Zikopoulos, K., and Richardson, D. W. (1992). Differential contribution of leucocytes and spermatozoa to the generation of reactive oxygen species in the ejaculates of oligozoospermic patients and fertile donors. J. Reprod. Fertil. 94, 451–462.
Differential contribution of leucocytes and spermatozoa to the generation of reactive oxygen species in the ejaculates of oligozoospermic patients and fertile donors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XktVGnuro%3D&md5=0f2963f9fa0ee14bc24b4fdf7157bdd9CAS | 1317451PubMed |

Aitken, R. J., Buckingham, D., and Harkiss, D. (1993a). Use of a xanthine oxidase free radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa. J. Reprod. Fertil. 97, 441–450.
Use of a xanthine oxidase free radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXkt1antLY%3D&md5=2e54da6e7a2db3f4084afd973aa351cbCAS | 8388958PubMed |

Aitken, R. J., Harkiss, D., and Buckingham, D. (1993b). Relationship between iron-catalysed lipid peroxidation potential and human sperm function. J. Reprod. Fertil. 98, 257–265.
Relationship between iron-catalysed lipid peroxidation potential and human sperm function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXltFCgt7s%3D&md5=d9a9916a7818b1c023bf0f467734a1f2CAS | 8345470PubMed |

Aitken, R. J., Harkiss, D., and Buckingham, D. W. (1993c). Analysis of lipid peroxidation mechanisms in human spermatozoa. Mol. Reprod. Dev. 35, 302–315.
Analysis of lipid peroxidation mechanisms in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXmsVejsbk%3D&md5=4324b444a894e8dba40a4e0899d56949CAS | 8352936PubMed |

Aitken, R. J., Paterson, M., Fisher, H., Buckingham, D. W., and van Duin, M. (1995). Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J. Cell Sci. 108, 2017–2025.
| 1:CAS:528:DyaK2MXls1Olt7Y%3D&md5=42a992c7ab1caef8481c057bcec54bfaCAS | 7544800PubMed |

Aitken, R. J., Buckingham, D. W., Harkiss, D., Paterson, M., Fisher, H., and Irvine, D. S. (1996). The extragenomic action of progesterone on human spermatozoa is influenced by redox regulated changes in tyrosine phosphorylation during capacitation. Mol. Cell. Endocrinol. 117, 83–93.
The extragenomic action of progesterone on human spermatozoa is influenced by redox regulated changes in tyrosine phosphorylation during capacitation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhsFOntLY%3D&md5=1c85a9d688ea4b6824e4a387deed793fCAS | 8734476PubMed |

Aitken, R. J., Fisher, H. M., Fulton, N., Gomez, E., Knox, W., Lewis, B., and Irvine, S. (1997). 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. 47, 468–482.
Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkt1Cjsbs%3D&md5=c85dc205527617368bafa548cd57c75eCAS | 9211432PubMed |

Aitken, R. J., Gordon, E., Harkiss, D., Twigg, J. P., Milne, P., Jennings, Z., and Irvine, D. S. (1998). Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol. Reprod. 59, 1037–1046.
Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmvFyqu74%3D&md5=ee0c7e0099d683fe80528b365d2f83bbCAS | 9780307PubMed |

Aitken, R. J., De Iuliis, G. N., Finnie, J. M., Hedges, A., and McLachlan, R. I. (2010). Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria. Hum. Reprod. 25, 2415–2426.
Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFyltLjN&md5=81c19d0350fc215fddfd14b7f781f24bCAS | 20716559PubMed |

Aitken, R. J., Whiting, S., De Iuliis, G. N., McClymont, S., Mitchell, L. A., and Baker, M. A. (2012). Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J. Biol. Chem. 287, 33 048–33 060.
Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlyqsrfF&md5=5acc14e894f8f45ec48ecd9c16baca8fCAS |

Aitken, R. J., Finnie, J. M., Muscio, L., Whiting, S., Connaughton, H. S., Kuczera, L., Rothkirch, T. B., and De Iuliis, G. N. (2014a). Potential importance of transition metals in the induction of DNA damage by sperm preparation media. Hum. Reprod. 29, 2136–2147.
Potential importance of transition metals in the induction of DNA damage by sperm preparation media.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC2M%2FjsFGisw%3D%3D&md5=8257f883726bb5e8fa9e7ae0ceb60554CAS | 25141857PubMed |

Aitken, R. J., Smith, T. B., Jobling, M. S., Baker, M. A., and De Iuliis, G. N. (2014b). Oxidative stress and male reproductive health. Asian J. Androl. 16, 31–38.
Oxidative stress and male reproductive health.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlajs7jM&md5=17bc65194a0f04720b6b83d93aef5025CAS | 24369131PubMed |

Aitken, J. B., Naumovski, N., Grupen, C. G., Gibb, Z., and Aitken, R. J. (2015a). Characterization of an l-amino acid oxidase in equine spermatozoa. Biol. Reprod. 92, 125.
Characterization of an l-amino acid oxidase in equine spermatozoa.Crossref | GoogleScholarGoogle Scholar | 25740544PubMed |

Aitken, R. J., Baker, M. A., and Nixon, B. (2015b). Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress? Asian J. Androl. 17, 633–639.
Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?Crossref | GoogleScholarGoogle Scholar | 25999358PubMed |

Alvarez, J. G., Touchstone, J. C., Blasco, L., and Storey, B. T. (1987). Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J. Androl. 8, 338–348.
| 1:CAS:528:DyaL2sXmtFGhtb4%3D&md5=2a8f0d2f88a7de782fe0d72a5a75873fCAS | 2822642PubMed |

Baker, M. A., Krutskikh, A., Curry, B. J., McLaughlin, E. A., and Aitken, R. J. (2004). Identification of cytochrome P450-reductase as the enzyme responsible for NADPH-dependent lucigenin and tetrazolium salt reduction in rat epididymal sperm preparations. Biol. Reprod. 71, 307–318.
Identification of cytochrome P450-reductase as the enzyme responsible for NADPH-dependent lucigenin and tetrazolium salt reduction in rat epididymal sperm preparations.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXltFKku7k%3D&md5=0b881451c0cb09fad902ab491eaeeef7CAS | 15031143PubMed |

Baker, M. A., Krutskikh, A., Curry, B. J., Hetherington, L., and Aitken, R. J. (2005). Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa. Biol. Reprod. 73, 334–342.
Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXms1yqsLs%3D&md5=52166d673439b4fa8fbe61374f298df3CAS | 15858218PubMed |

Baker, M. A., Weinberg, A., Hetherington, L., Villaverde, A. I., Velkov, T., Baell, J., and Gordon, C. P. (2015). Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function. Biol. Reprod. 92, 108.
Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function.Crossref | GoogleScholarGoogle Scholar | 25673561PubMed |

Bakos, H. W., Mitchell, M., Setchell, B. P., and Lane, M. (2011). The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model. Int. J. Androl. 34, 402–410.
The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlOlu7fP&md5=29743890e6a416f5a1a7c6e1d8d8065cCAS | 20649934PubMed |

Bánfi, B., Molnár, G., Maturana, A., Steger, K., Hegedûs, B., Demaurex, N., and Krause, K. H. (2001). A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J. Biol. Chem. 276, 37 594–37 601.
A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes.Crossref | GoogleScholarGoogle Scholar |

Barron, E. S. G., Flood, V., and Gasvoda, B. (1949). The effect of hydrogen peroxide and of X-ray irradiated sea water on the respiration of sea urchin sperm and eggs. Biol. Bull. 97, 51–56.
The effect of hydrogen peroxide and of X-ray irradiated sea water on the respiration of sea urchin sperm and eggs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaH1MXltFOlsA%3D%3D&md5=81fc4606103cf05de32198ae5c821f8eCAS |

Bejarano, I., Monllor, F., Marchena, A. M., Ortiz, A., Lozano, G., Jiménez, M. I., Gaspar, P., García, J. F., Pariente, J. A., Rodríguez, A. B., and Espino, J. (2014). Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa. J. Pineal Res. 57, 333–339.
Exogenous melatonin supplementation prevents oxidative stress-evoked DNA damage in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsF2ntbnK&md5=5d4a7ea428e16f384466020467ced270CAS | 25187254PubMed |

Bize, I., Santander, G., Cabello, P., Driscoll, D., and Sharpe, C. (1991). Hydrogen peroxide is involved in hamster sperm capacitation in vitro. Biol. Reprod. 44, 398–403.
Hydrogen peroxide is involved in hamster sperm capacitation in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXhsVSlsr0%3D&md5=fc024c1590d8144036fa08d6d7d66c36CAS | 2015358PubMed |

Boekelheide, K. (2005). Mechanisms of toxic damage to spermatogenesis. J. Natl Cancer Inst. Monogr. 2005, 6–8.
Mechanisms of toxic damage to spermatogenesis.Crossref | GoogleScholarGoogle Scholar |

Burrello, N., Calogero, A. E., Perdichizzi, A., Salmeri, M., D’Agata, R., and Vicari, E. (2004). Inhibition of oocyte fertilization by assisted reproductive techniques and increased sperm DNA fragmentation in the presence of Candida albicans: a case report. Reprod. Biomed. Online 8, 569–573.
Inhibition of oocyte fertilization by assisted reproductive techniques and increased sperm DNA fragmentation in the presence of Candida albicans: a case report.Crossref | GoogleScholarGoogle Scholar | 15151722PubMed |

Burruel, V., Klooster, K. L., Chitwood, J., Ross, P. J., and Meyers, S. A. (2013). Oxidative damage to rhesus macaque spermatozoa results in mitotic arrest and transcript abundance changes in early embryos. Biol. Reprod. 89, 72.
Oxidative damage to rhesus macaque spermatozoa results in mitotic arrest and transcript abundance changes in early embryos.Crossref | GoogleScholarGoogle Scholar | 23904511PubMed |

Chabory, E., Damon, C., Lenoir, A., Kauselmann, G., Kern, H., Zevnik, B., Garrel, C., Saez, F., Cadet, R., Henry-Berger, J., Schoor, M., Gottwald, U., Habenicht, U., Drevet, J. R., and Vernet, P. (2009). Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J. Clin. Invest. 119, 2074–2085.
| 1:CAS:528:DC%2BD1MXosVCrs7k%3D&md5=d2250ccb3f9e35ec5bc4c19435db1452CAS | 19546506PubMed |

Chen, S. J., Allam, J. P., Duan, Y. G., and Haidl, G. (2013). Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch. Gynecol. Obstet. 288, 191–199.
Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXps1ynurw%3D&md5=44c1aa88a6bf74aa881c9a0f8100d9a5CAS | 23543240PubMed |

De Iuliis, G. N., Newey, R. J., King, B. V., and Aitken, R. J. (2009a). Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro. PLoS One 4, e6446.
Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro.Crossref | GoogleScholarGoogle Scholar | 19649291PubMed |

De Iuliis, G. N., Thomson, L. K., Mitchell, L. A., Finnie, J. M., Koppers, A. J., Hedges, A., Nixon, B., and Aitken, R. J. (2009b). DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress. Biol. Reprod. 81, 517–524.
DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVChu7%2FE&md5=00670de75d471a0ddb62762dcdbcf894CAS | 19494251PubMed |

de Lamirande, E., and Gagnon, C. (1993a). Human sperm hyperactivation and capacitation as parts of an oxidative process. Free Radic. Biol. Med. 14, 157–166.
Human sperm hyperactivation and capacitation as parts of an oxidative process.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXitFSisb4%3D&md5=d34970438c37b12c265dec3670609f4fCAS | 8381103PubMed |

de Lamirande, E., and Gagnon, C. (1993b). A positive role for the superoxide anion in triggering hyperactivation and capacitation of human spermatozoa. Int. J. Androl. 16, 21–25.
A positive role for the superoxide anion in triggering hyperactivation and capacitation of human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXks1yrs7g%3D&md5=26c63f283956cb1db06c5b4c7fec5603CAS | 8385650PubMed |

Delbès, G., Hales, B. F., and Robaire, B. (2010). Toxicants and human sperm chromatin integrity. Mol. Hum. Reprod. 16, 14–22.
Toxicants and human sperm chromatin integrity.Crossref | GoogleScholarGoogle Scholar | 19812089PubMed |

Donà, G., Fiore, C., Andrisani, A., Ambrosini, G., Brunati, A., Ragazzi, E., Armanini, D., Bordin, L., and Clari, G. (2011). Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system. Hum. Reprod. 26, 3264–3273.
Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system.Crossref | GoogleScholarGoogle Scholar | 21940394PubMed |

du Plessis, S. S., Agarwal, A., Mohanty, G., and van der Linde, M. (2015). Oxidative phosphorylation versus glycolysis: what fuel do spermatozoa use? Asian J. Androl. 17, 230–235.
Oxidative phosphorylation versus glycolysis: what fuel do spermatozoa use?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXkt1Snt7s%3D&md5=2cf80d10f97a7051a6cfad858432712dCAS | 25475660PubMed |

Erkekoglu, P., Rachidi, W., Yuzugullu, O. G., Giray, B., Favier, A., Ozturk, M., and Hincal, F. (2010). Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol. Appl. Pharmacol. 248, 52–62.
Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGjurfF&md5=fb521fb4536427458902f4cdf88969f7CAS | 20659492PubMed |

Evans, T. C. (1947). Effects of hydrogen peroxide produced in the medium by radiation of spermatozoa of Arbacia punctulata. Biol. Bull. 92, 99–109.
Effects of hydrogen peroxide produced in the medium by radiation of spermatozoa of Arbacia punctulata.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaH2sXjvVSkuw%3D%3D&md5=e5c7e8359b11704ff53776d3fab69858CAS | 20294094PubMed |

Evenson, D. P., and Wixon, R. (2005). Environmental toxicants cause sperm DNA fragmentation as detected by the sperm chromatin structure assay (SCSA). Toxicol. Appl. Pharmacol. 207, 532–537.
Environmental toxicants cause sperm DNA fragmentation as detected by the sperm chromatin structure assay (SCSA).Crossref | GoogleScholarGoogle Scholar | 15987647PubMed |

Fariello, R. M., Pariz, J. R., Spaine, D. M., Cedenho, A. P., Bertolla, R. P., and Fraietta, R. (2012). Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. BJU Int. 110, 863–867.
Association between obesity and alteration of sperm DNA integrity and mitochondrial activity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1Cgt7jP&md5=d7e5243f8b40d859391f631802329699CAS | 22300410PubMed |

Fraga, C. G., Motchnik, P. A., Shigenaga, M. K., Helbock, H. J., Jacob, R. A., and Ames, B. N. (1991). Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl Acad. Sci. USA 88, 11 003–11 006.
Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xlsl2lug%3D%3D&md5=8d80819742fd876b41744528132b293bCAS |

Fraga, C. G., Motchnik, P. A., Wyrobek, A. J., Rempel, D. M., and Ames, B. N. (1996). Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat. Res. 351, 199–203.
Smoking and low antioxidant levels increase oxidative damage to sperm DNA.Crossref | GoogleScholarGoogle Scholar | 8622715PubMed |

Fujita, Y., Mihara, T., Okazaki, T., Shitanaka, M., Kushino, R., Ikeda, C., Negishi, H., Liu, Z., Richards, J. S., and Shimada, M. (2011). Toll-like receptors (TLR) 2 and 4 on human sperm recognize bacterial endotoxins and mediate apoptosis. Hum. Reprod. 26, 2799–2806.
Toll-like receptors (TLR) 2 and 4 on human sperm recognize bacterial endotoxins and mediate apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SiurrN&md5=27a608f6de795179ab4ea4d640736fdbCAS | 21775336PubMed |

Ghani, E., Keshtgar, S., Habibagahi, M., Ghannadi, A., and Kazeroni, M. (2013). Expression of NOX5 in human teratozoospermia compared to normozoospermia. Andrologia 45, 351–356.
Expression of NOX5 in human teratozoospermia compared to normozoospermia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtl2ltbjP&md5=a1fec158a2810200f9576ccd78859deaCAS | 23030296PubMed |

Gharagozloo, P., and Aitken, R. J. (2011). The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum. Reprod. 26, 1628–1640.
The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy.Crossref | GoogleScholarGoogle Scholar | 21546386PubMed |

Ghosh, D., Das, U. B., and Misro, M. (2002). Protective role of alpha-tocopherol–succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic. Res. 36, 1209–1218.
Protective role of alpha-tocopherol–succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xos1Sis7g%3D&md5=807cc86de0bb882b7e6f79d83aa83a53CAS | 12592673PubMed |

Gibb, Z., Lambourne, S. R., and Aitken, R. J. (2014). The paradoxical relationship between stallion fertility and oxidative stress. Biol. Reprod. 91, 77.
The paradoxical relationship between stallion fertility and oxidative stress.Crossref | GoogleScholarGoogle Scholar | 25078685PubMed |

Grizard, G., Ouchchane, L., Roddier, H., Artonne, C., Sion, B., Vasson, M. P., and Janny, L. (2007). In vitro alachlor effects on reactive oxygen species generation, motility patterns and apoptosis markers in human spermatozoa. Reprod. Toxicol. 23, 55–62.
In vitro alachlor effects on reactive oxygen species generation, motility patterns and apoptosis markers in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXisValuw%3D%3D&md5=d2f4759cbe16c979ee604db38701398bCAS | 17049205PubMed |

Herrero, M. B., de Lamirande, E., and Gagnon, C. (2001). Tyrosine nitration in human spermatozoa: a physiological function of peroxynitrite, the reaction product of nitric oxide and superoxide. Mol. Hum. Reprod. 7, 913–921.
Tyrosine nitration in human spermatozoa: a physiological function of peroxynitrite, the reaction product of nitric oxide and superoxide.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnvVGhsbk%3D&md5=d83a4d0cae73a064caf33869b4b06eecCAS | 11574660PubMed |

Hosken, D. J., and Hodgson, D. J. (2014). Why do sperm carry RNA? Relatedness, conflict, and control. Trends Ecol. Evol. 29, 451–455.
Why do sperm carry RNA? Relatedness, conflict, and control.Crossref | GoogleScholarGoogle Scholar | 24916312PubMed |

Houston, B., Curry, B., and Aitken, R. J. (2015). Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function. Reproduction 149, 587–596.
Human spermatozoa possess an IL4I1 l-amino acid oxidase with a potential role in sperm function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtFamtbzF&md5=232c53eb3a3972c83767ff7895cf27a6CAS | 25767141PubMed |

Hull, M. G. R., Glazener, C. M. A., Kelly, N. J., Conway, D. I., Foster, P. A., Hunton, R. A., Coulson, C., Lambert, P. A., Watt, E. M., and Desai, K. M. (1985). Population study of causes, treatment and outcome of infertility. Br. Med. J. (Clin. Res. Ed.) 291, 1693–1697.
Population study of causes, treatment and outcome of infertility.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL28%2FnvVCnsw%3D%3D&md5=b3ffc16bbbbc2fd8796bce266230a836CAS |

Irvine, D. S., Twigg, J. P., Gordon, E. L., Fulton, N., Milne, P. A., and Aitken, R. J. (2000). DNA integrity in human spermatozoa: relationships with semen quality. J. Androl. 21, 33–44.
| 1:STN:280:DC%2BD3c7jtl2ktQ%3D%3D&md5=36e5612f3e416a2d39d379b23b20f3f8CAS | 10670517PubMed |

Jones, R., Mann, T., and Sherins, R. J. (1978). Adverse effects of peroxidized lipid on human spermatozoa. Proc. R. Soc. Lond. B Biol. Sci. 201, 413–417.
Adverse effects of peroxidized lipid on human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXltVCnu7Y%3D&md5=09c3cee6a500d498887d8cbf8b354f19CAS |

Jones, R., Mann, T., and Sherins, R. J. (1979). Peroxidative breakdown of phospholipids in human spermatozoa: spermicidal effects of fatty acid peroxides and protective action of seminal plasma. Fertil. Steril. 31, 531–537.
| 1:CAS:528:DyaE1MXksFegtbw%3D&md5=d33336e8d68f7a7b4e1b514582b58ad1CAS | 446777PubMed |

Kao, S. H., Chao, H. T., Chen, H. W., Hwang, T. I., Liao, T. L., and Wei, Y. H. (2008). Increase of oxidative stress in human sperm with lower motility. Fertil. Steril. 89, 1183–1190.
Increase of oxidative stress in human sperm with lower motility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1ylsr7I&md5=b4e5e14bb150cbec1596c967e95f380eCAS | 17669405PubMed |

Katen, A. L., and Roman, S. D. (2015). The genetic consequences of paternal acrylamide exposure and potential for amelioration. Mutat. Res. 777, 91–100.
The genetic consequences of paternal acrylamide exposure and potential for amelioration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXnt1Skt78%3D&md5=99306b74c04c8b74e7499c7c469a7b74CAS | 25989052PubMed |

Koppers, A. J., De Iuliis, G. N., Finnie, J. M., McLaughlin, E. A., and Aitken, R. J. (2008). Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. J. Clin. Endocrinol. Metab. 93, 3199–3207.
Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXpvVOlsLw%3D&md5=7ffe63557cb620e4b6173298bca82805CAS | 18492763PubMed |

Koppers, A. J., Mitchell, L. A., Wang, P., Lin, M., and Aitken, R. J. (2011). Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem. J. 436, 687–698.
Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXntV2gsLY%3D&md5=1e93c207a3cb407901ace65469187a58CAS | 21470189PubMed |

Lagos-Cabré, R., and Moreno, R. D. (2012). Contribution of environmental pollutants to male infertility: a working model of germ cell apoptosis induced by plasticizers. Biol. Res. 45, 5–14.
Contribution of environmental pollutants to male infertility: a working model of germ cell apoptosis induced by plasticizers.Crossref | GoogleScholarGoogle Scholar | 22688978PubMed |

Lane, M., McPherson, N. O., Fullston, T., Spillane, M., Sandeman, L., Kang, W. X., and Zander-Fox, D. L. (2014). Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring. PLoS One 9, e100832.
Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring.Crossref | GoogleScholarGoogle Scholar | 25006800PubMed |

Liang, R., Senturker, S., Shi, X., Bal, W., Dizdaroglu, M., and Kasprzak, K. S. (1999). Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage. Carcinogenesis 20, 893–898.
Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXjtVanur0%3D&md5=de40cf156d367e85e26de9c40099d7faCAS | 10334208PubMed |

Lundbaek, J. A., and Andersen, O. S. (1994). Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers. J. Gen. Physiol. 104, 645–673.
Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXitFCrtLw%3D&md5=d8f2675156293840b30143ddf8b3943fCAS | 7530766PubMed |

MacLeod, J. (1943). The role of oxygen in the metabolism and motility of human spermatozoa. Am. J. Physiol. 138, 512–518.
| 1:CAS:528:DyaH3sXhsVyktg%3D%3D&md5=9f02dd2aa96e1c0c2a3ba35c23641e14CAS |

Metzler-Guillemain, C., Victorero, G., Lepoivre, C., Bergon, A., Yammine, M., Perrin, J., Sari-Minodier, I., Boulanger, N., Rihet, P., and Nguyen, C. (2015). Sperm mRNAs and microRNAs as candidate markers for the impact of toxicants on human spermatogenesis: an application to tobacco smoking. Syst Biol Reprod Med 61, 139–149.
Sperm mRNAs and microRNAs as candidate markers for the impact of toxicants on human spermatogenesis: an application to tobacco smoking.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXpt1Knt7o%3D&md5=a9a0b5193a3e5d67d8986c3bb413eb49CAS | 25821920PubMed |

Moazamian, R., Polhemus, A., Connaughton, H., Fraser, B., Whiting, S., Gharagozloo, P., and Aitken, R. J. (2015). Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation. Mol. Hum. Reprod. 21, 502–515.
Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation.Crossref | GoogleScholarGoogle Scholar | 25837702PubMed |

Morielli, T., and O’Flaherty, C. (2015). Oxidative stress impairs function and increases redox protein modifications in human spermatozoa. Reproduction 149, 113–123.
Oxidative stress impairs function and increases redox protein modifications in human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 25385721PubMed |

Morimoto, H., Iwata, K., Ogonuki, N., Inoue, K., Atsuo, O., Kanatsu-Shinohara, M., Morimoto, T., Yabe-Nishimura, C., and Shinohara, T. (2013). ROS are required for mouse spermatogonial stem cell self-renewal. Cell Stem Cell 12, 774–786.
ROS are required for mouse spermatogonial stem cell self-renewal.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXptFOhtro%3D&md5=0a3c00d440ac58fc171da7e1b54b33c1CAS | 23746981PubMed |

Muratori, M., Tamburrino, L., Marchiani, S., Cambi, M., Olivito, B., Azzari, C., Forti, G., and Baldi, E. (2015). Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress. Mol. Med. 21, 109–122.
Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXpvFKhsbc%3D&md5=056263b2c92db0964eee4c8cc2f1426aCAS | 25786204PubMed |

Musset, B., Clark, R. A., DeCoursey, T. E., Petheo, G. L., Geiszt, M., Chen, Y., Cornell, J. E., Eddy, C. A., Brzyski, R. G., and El Jamali, A. (2012). NOX5 in human spermatozoa: expression, function, and regulation. J. Biol. Chem. 287, 9376–9388.
NOX5 in human spermatozoa: expression, function, and regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjvVegsL8%3D&md5=3960cacfd0a5bde7cb0e0894b5051265CAS | 22291013PubMed |

Nakamura, H., Kimura, T., Nakajima, A., Shimoya, K., Takemura, M., Hashimoto, K., Isaka, S., Azuma, C., Koyama, M., and Murata, Y. (2002). Detection of oxidative stress in seminal plasma and fractionated sperm from subfertile male patients. Eur. J. Obstet. Gynecol. Reprod. Biol. 105, 155–160.
Detection of oxidative stress in seminal plasma and fractionated sperm from subfertile male patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnvVKnu7Y%3D&md5=999b2b6279310bbd5bac0d7bd9e22422CAS | 12381479PubMed |

Nishikawa, T., Tomori, Y., Yamashita, S., and Shimizu, S. (1989). Inhibition of Na+,K+-ATPase activity by phospholipase A2 and several lysophospholipids: possible role of phospholipase A2 in noradrenaline release from cerebral cortical synaptosomes. J. Pharm. Pharmacol. 41, 450–458.
Inhibition of Na+,K+-ATPase activity by phospholipase A2 and several lysophospholipids: possible role of phospholipase A2 in noradrenaline release from cerebral cortical synaptosomes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXlt1OmtL0%3D&md5=c819c224b92ffa196bcb1096bc9f49c7CAS | 2570849PubMed |

Noblanc, A., Damon-Soubeyrand, C., Karrich, B., Henry-Berger, J., Cadet, R., Saez, F., Guiton, R., Janny, L., Pons-Rejraji, H., Alvarez, J. G., Drevet, J. R., and Kocer, A. (2013). DNA oxidative damage in mammalian spermatozoa: where and why the male nucleus is impacted? Free Radic. Biol. Med. 65, 719–723.
DNA oxidative damage in mammalian spermatozoa: where and why the male nucleus is impacted?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvFymu7vL&md5=05c9eea1f121a563e79d773c57176307CAS | 23954469PubMed |

O’Flaherty, C. (2014). Iatrogenic genetic damage of spermatozoa. Adv. Exp. Med. Biol. 791, 117–135.
Iatrogenic genetic damage of spermatozoa.Crossref | GoogleScholarGoogle Scholar | 23955676PubMed |

Ohno, M., Sakumi, K., Fukumura, R., Furuichi, M., Iwasaki, Y., Hokama, M., Ikemura, T., Tsuzuki, T., Gondo, Y., and Nakabeppu, Y. (2014). 8-Oxoguanine causes spontaneous de novo germline mutations in mice. Sci. Rep. 4, 4689.
8-Oxoguanine causes spontaneous de novo germline mutations in mice.Crossref | GoogleScholarGoogle Scholar | 24732879PubMed |

Ostermeier, G. C., Goodrich, R. J., Moldenhauer, J. S., Diamond, M. P., and Krawetz, S. A. (2005). A suite of novel human spermatozoal RNAs. J. Androl. 26, 70–74.
| 1:CAS:528:DC%2BD2MXmsFWnsw%3D%3D&md5=69b4f1ff8743842dbc9efe09903f5756CAS | 15611569PubMed |

Palmer, N. O., Bakos, H. W., Owens, J. A., Setchell, B. P., and Lane, M. (2012). Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am. J. Physiol. Endocrinol. Metab. 302, E768–E780.
Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xmsl2gtrg%3D&md5=ff78c15e91014a6171ab3075bacd74c1CAS | 22252945PubMed |

Prescott, J., Du, M., Wong, J. Y., Han, J., and De Vivo, I. (2012). Paternal age at birth is associated with offspring leukocyte telomere length in the Nurses’ Health Study. Hum. Reprod. 27, 3622–3631.
Paternal age at birth is associated with offspring leukocyte telomere length in the Nurses’ Health Study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslKrsLvN&md5=95b7df673a11dd2a0b9a529e81cfd5d6CAS | 22940768PubMed |

Reichart, M., Kahane, I., and Bartoov, B. (2000). In vivo and in vitro impairment of human and ram sperm nuclear chromatin integrity by sexually transmitted Ureaplasma urealyticum infection. Biol. Reprod. 63, 1041–1048.
In vivo and in vitro impairment of human and ram sperm nuclear chromatin integrity by sexually transmitted Ureaplasma urealyticum infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmslyltLc%3D&md5=36ca095ca0385c6bcbda5bf4c523ed0cCAS | 10993825PubMed |

Rivlin, J., Mendel, J., Rubinstein, S., Etkovitz, N., and Breitbart, H. (2004). Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol. Reprod. 70, 518–522.
Role of hydrogen peroxide in sperm capacitation and acrosome reaction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXnsl2itA%3D%3D&md5=4b7d8251e0fd8a37f84860e18383ac10CAS | 14561655PubMed |

Rodriguez, P. C., and Beconi, M. T. (2009). Peroxynitrite participates in mechanisms involved in capacitation of cryopreserved cattle. Anim. Reprod. Sci. 110, 96–107.
Peroxynitrite participates in mechanisms involved in capacitation of cryopreserved cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlGgsLvM&md5=e5976cd53790832b43a61fd33b7613dbCAS | 18262738PubMed |

Sakamoto, Y., Ishikawa, T., Kondo, Y., Yamaguchi, K., and Fujisawa, M. (2008). The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 101, 1547–1552.
The assessment of oxidative stress in infertile patients with varicocele.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXosVWjtbY%3D&md5=335ac8a235f5d5245d2c9c3986519190CAS | 18294306PubMed |

Sanocka, D., Miesel, R., Jedrzejczak, P., and Kurpisz, M. K. (1996). Oxidative stress and male infertility. J. Androl. 17, 449–454.
| 1:STN:280:DyaK2s%2FksVKgug%3D%3D&md5=46c40fa1c351d35105813f770927fd2eCAS | 8889709PubMed |

Santiso, R., Tamayo, M., Gosálvez, J., Johnston, S., Mariño, A., Fernández, C., Losada, C., and Fernández, J. L. (2012). DNA fragmentation dynamics allows the assessment of cryptic sperm damage in human: evaluation of exposure to ionizing radiation, hyperthermia, acidic pH and nitric oxide. Mutat. Res. 734, 41–49.
DNA fragmentation dynamics allows the assessment of cryptic sperm damage in human: evaluation of exposure to ionizing radiation, hyperthermia, acidic pH and nitric oxide.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xlt1KrtL4%3D&md5=50ee6d5be3c2c4f9d8c32fa4d474ec47CAS | 22469500PubMed |

Sharma, R. K., and Agarwal, A. (1996). Role of reactive oxygen species in male infertility. Urology 48, 835–850.
Role of reactive oxygen species in male infertility.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2s7ivFWhtw%3D%3D&md5=03ed5ca7d4c96f886f1b8823ef0aefbcCAS | 8973665PubMed |

Shen, H., and Ong, C. (2000). Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic. Biol. Med. 28, 529–536.
Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhslaks7c%3D&md5=21352dc8272e0eb8876df62f7590f56dCAS | 10719234PubMed |

Showell, M. G., Mackenzie-Proctor, R., Brown, J., Yazdani, A., Stankiewicz, M. T., and Hart, R. J. (2014). Antioxidants for male subfertility. Cochrane Database Syst. Rev. 12, CD007411.
| 25504418PubMed |

Shukla, K. K., Mahdi, A. A., and Rajender, S. (2012). Apoptosis, spermatogenesis and male infertility. Front. Biosci. (Elite Ed.) E4, 746–754.
Apoptosis, spermatogenesis and male infertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XjtVKjsro%3D&md5=8cdecfa5b75038c3f161419778d4ff80CAS |

Sibirtsev, J. T., Shastina, V. V., Menzorova, N. I., Makarieva, T. N., and Rasskazov, V. (2011). A Ca2+, Mg2+-dependent DNase involvement in apoptotic effects in spermatozoa of sea urchin Strongylocentrotus intermedius induced by two-headed sphingolipid, rhizochalin. Mar. Biotechnol. (NY) 13, 536–543.
A Ca2+, Mg2+-dependent DNase involvement in apoptotic effects in spermatozoa of sea urchin Strongylocentrotus intermedius induced by two-headed sphingolipid, rhizochalin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmslOrtLs%3D&md5=0204ad6d8c984189d495284c9c798448CAS | 20938797PubMed |

Simões, R., Feitosa, W. B., Siqueira, A. F., Nichi, M., Paula-Lopes, F. F., Marques, M. G., Peres, M. A., Barnabe, V. H., Visintin, J. A., and Assumpção, M. E. (2013). Influence of bovine sperm DNA fragmentation and oxidative stress on early embryo in vitro development outcome. Reproduction 146, 433–441.
Influence of bovine sperm DNA fragmentation and oxidative stress on early embryo in vitro development outcome.Crossref | GoogleScholarGoogle Scholar | 23940385PubMed |

Singh, N. P., and Stephens, R. E. (1998). X-Ray induced DNA double-strand breaks in human sperm. Mutagenesis 13, 75–79.
X-Ray induced DNA double-strand breaks in human sperm.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXpsVertw%3D%3D&md5=a253fa271accd628aa7a5227e05884c3CAS | 9491398PubMed |

Singh, N. P., Muller, C. H., and Berger, R. E. (2003). Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil. Steril. 80, 1420–1430.
Effects of age on DNA double-strand breaks and apoptosis in human sperm.Crossref | GoogleScholarGoogle Scholar | 14667878PubMed |

Smith, T. B., De Iuliis, G. N., Lord, T., and Aitken, R. J. (2013a). The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line. Reproduction 146, 253–262.
The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVaiu77K&md5=c6475b716438097ac1c66f1c941d4f6eCAS | 23813448PubMed |

Smith, T. B., Dun, M. D., Smith, N. D., Curry, B. J., Connaughton, H. S., and Aitken, R. J. (2013b). The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1. J. Cell Sci. 126, 1488–1497.
The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXpsFKjsLk%3D&md5=909bebbe79f522998c71586ad6d51faaCAS | 23378024PubMed |

Sotolongo, B., Huang, T. T., Isenberger, E., and Ward, W. S. (2005). An endogenous nuclease in hamster, mouse, and human spermatozoa cleaves DNA into loop-sized fragments. J. Androl. 26, 272–280.
| 1:CAS:528:DC%2BD2MXis1Slu7s%3D&md5=4044b7dc4f3fa8f7a3ef03326ed65707CAS | 15713834PubMed |

Soubry, A. (2015). Epigenetic inheritance and evolution: a paternal perspective on dietary influences. Prog. Biophys. Mol. Biol. 118, 79–85.
Epigenetic inheritance and evolution: a paternal perspective on dietary influences.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXksV2iur0%3D&md5=c4f60a5e25c790c90e927aee9999f824CAS | 25769497PubMed |

Tosic, J., and Walton, A. (1946). Formation of hydrogen peroxide by spermatozoa and its inhibitory effect on respiration. Nature 158, 485.
Formation of hydrogen peroxide by spermatozoa and its inhibitory effect on respiration.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaH2sXhtlKmuw%3D%3D&md5=befe530082046a4d7e665fe96c851260CAS | 20999112PubMed |

Tosic, J., and Walton, A. (1950). Metabolism of spermatozoa. The formation and elimination of hydrogen peroxide by spermatozoa and effects on motility and survival. Biochem. J. 47, 199–212.
| 1:CAS:528:DyaG3MXktFKn&md5=40d44630d5b154f934df81100356ed26CAS | 14791344PubMed |

van Kuijk, F. J., Handelman, G. J., and Dratz, E. A. (1985). Consecutive action of phospholipase A2 and glutathione peroxidase is required for reduction of phospholipid hydroperoxides and provides a convenient method to determine peroxide values in membranes. J. Free Radic. Biol. Med. 1, 421–427.
Consecutive action of phospholipase A2 and glutathione peroxidase is required for reduction of phospholipid hydroperoxides and provides a convenient method to determine peroxide values in membranes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XlvVKrtL0%3D&md5=76af3ab55b13d1021de0fb5f4e785e0eCAS | 3837805PubMed |

Vernet, P., Fulton, N., Wallace, C., and Aitken, R. J. (2001). Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa. Biol. Reprod. 65, 1102–1113.
Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnt1Cms74%3D&md5=a0920a7c6b6d12ec03aec9b98613af7bCAS | 11566731PubMed |

Wang, X., Sharma, R. K., Sikka, S. C., Thomas, A. J., Falcone, T., and Agarwal, A. (2003). Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility. Fertil. Steril. 80, 531–535.
Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility.Crossref | GoogleScholarGoogle Scholar | 12969693PubMed |

Weir, C. P., and Robaire, B. (2007). Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat. J. Androl. 28, 229–240.
Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive oxygen species production during aging in the Brown Norway rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjslertb0%3D&md5=37fe52845fc04d3bb8078c28b8117134CAS | 17021340PubMed |

Zalata, A., Hafez, T., Mahmoud, A., and Comhaire, F. (1995). Relationship between resazurin reduction test, reactive oxygen species generation, and gamma-glutamyltransferase. Hum. Reprod. 10, 1136–1140.
| 1:CAS:528:DyaK2MXnt1OmsLc%3D&md5=67ef7c60bc2f543815d7f2d9eabe38c1CAS | 7657753PubMed |

Zhou, D., Wang, H., Zhang, J., Gao, X., Zhao, W., and Zheng, Y. (2010). Di-n-butyl phthalate (DBP) exposure induces oxidative damage in testes of adult rats. Syst. Biol. Reprod. Med. 56, 413–419.
Di-n-butyl phthalate (DBP) exposure induces oxidative damage in testes of adult rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVansL3M&md5=9886e8dfdfadf329c52a76b4a989bd01CAS | 20883123PubMed |

Zribi, N., Chakroun, N. F., Ben Abdallah, F., Elleuch, H., Sellami, A., Gargouri, J., Rebai, T., Fakhfakh, F., and Keskes, L. A. (2012). Effect of freezing–thawing process and quercetin on human sperm survival and DNA integrity. Cryobiology 65, 326–331.
Effect of freezing–thawing process and quercetin on human sperm survival and DNA integrity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhsFSntrzO&md5=231d9fb2d02731176fb322e17614e562CAS | 23010483PubMed |