Animal Reproduction (AR)
Animal Reproduction (AR)
Conference Paper

Impacts of oxidative stress on bovine sperm function and subsequent in vitro embryo development

Heinrich Bollwein, Lilli Bittner

Downloads: 2
Views: 841


Low levels of reactive oxygen species (ROS) in sperm are essential for various sperm functions such as capacitation, hyperactivation and acrosome reaction. However, increased synthesis of ROS or a disruption of antioxidative status (e.g. in cryopreserved sperm) can induce oxidative stress (OS). Sperm are particularly vulnerable to OS, as their plasma membrane contains large amounts of polyunsaturated fatty acids and they have limited antioxidative capacity (due to low cytoplasmic volume). Oxidative stress disturbs sperm function by damaging sperm proteins, lipids and DNA. Under relatively low OS sperm may retain their fertilizing ability, which might result in transfer of impaired paternal molecules (e.g. damaged DNA) to the fertilized oozyte. Oocytes can repair damaged paternal DNA, but only to a certain extent. Most embryos are either repaired (based on limited DNA damage in blastocysts) or eliminated (based on low percentage of blastocyst formation when sperm with damaged DNA is used for fertilization). However, some blastocysts had increases in both DNA damage and apoptosis, which could have important implications for subsequent development. In several studies, exogenous antioxidants improved quality of sperm exposed to oxidative stress and subsequent embryo development. However, there is still a knowledge gap regarding whether these alterations affect embryonic survival and further development to a live fetus and healthy offspring.


embryo development, Oxidative stress, sperm function.


Agarwal A, Saleh RA. 2002. Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am, 29:817-827.

Agarwal A, Majzoub A. 2017. Role of antioxidants in Assisted Reproductive Techniques. World J Mens Health, 35:77-93.

Aitken RJ, Clarkson J, Fishel S. 1989. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod. 41:183-197.

Aitken RJ, Baker M. 2006. Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol, 250:66-69.

Aitken RJ, Whiting S, De Iuliis GN, McClymont S, Mitchell LA, Baker MA. 2012. Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J Biol Chem, 287:33048-33060.

Aitken RJ. 2017. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol Reprod Dev, 84:1039-1052.

Asch R, Simerly C, Ord T, Ord VA, Schatten G. 1995. The stages at which human fertilization arrests: Microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans. Mol Hum Reprod, 1:239-248.

Ashwood-Smith M, Edwards R. 1996. Genetics and human conception DNA repair by oocytes. Mol Hum, 2:46-51.

Austin CR, Bishop MW. 1958. Capacitation of mammalian spermatozoa. Nature, 181:851.

Baker MA, Weinberg A, Hetherington L, Villaverde AI, Velkov T, Baell J, Gordon CP. 2015. Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function. Biol Reprod, 92:108.

Barton TS, Robaire B, Hales BF. 2007. DNA damage recognition in the rat zygote following chronic paternal cyclophosphamide exposure. Toxicol Sci, 100:495-503.

Bilodeau JF, Chatterjee S, Sirard, MA, Gagnon C. 2000. Levels of antioxidant defenses are decreased in bovine spermatozoa after a cycle of freezing. Mol Reprod Dev, 55:282-288.

Breen A, Murphy J. 1995. Reactions of oxyl radicals with DNA. Free Radic Biol Med, 18:1033-1077.

Burrows C, Muller J. 1998. Oxidative nucleobase modifications leading to strand scission. Chem Rev, 98:1109-1152.

Cadet J, Douki T, Gasparutto D, Ravanat J. 2003. Oxidative damage to DNA: formation, measurement and biochemical features. Mutat Res Mol Mech Mutagen, 531:5-23.

Celeste A, Fernandez-Capetillo O, Kruhlak MJ, Pilch DR, Staudt DW, Lee A, Bonner RF, Bonner WM, Nussenzweig A. 2003. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol, 5:675-679.

Cummins JM. 2001. Cytoplasmic inheritance and its implications for animal biotechnology. Theriogenology, 55:1381-1399.

Davies K. 1987. Protein damage and degradation by oxygen radicals. I. general aspects. J Biol Chem, 262:9895-9901.

de Assis PM, Castro LS, Siqueira AF, Delgado Jde C, Hamilton TR, Goissis MD, Mendes CM, Nichi M, Visintin JA, Assumpção ME. 2015. System for evaluation of oxidative stress on in-vitro-produced bovine embryos. Reprod Biomed Online, 31:577-580.

de Castro LS, de Assis PM, Siqueira AF, Hamilton TR, Mendes CM, Losano JD, Nichi M, Visintin JA, Assumpção ME. 2016. Sperm oxidative stress is detrimental to embryo development: A dose-dependent study model and a new and more sensitive oxidative status evaluation. Oxid Med Cell Longev, 8213071. DOI: 10.1155/2016/8213071.

De Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. 1997. Reactive oxygen species and sperm physiology. Rev Reprod, 2:48-54

Evans MD, Cooke MS (Eds). 2009. Oxidative damage to Nucleic Acids. New York, USA: Springer.

Finkel T, Holbrook N. 2000. Oxidants, oxidative stress and the biology of ageing. Nature, 408:239-247.

Freeman B, Crapo J. 1982. Biology of disease: free radicals and tissue injury. Lab Invest, 47:412-426.

Gardiner-Garden M, Ballesteros M, Gordon M, Tam PP. 1998. Histone- and protamine-DNA association: conservation of different patterns within the beta-globin domain in human sperm. Mol Cell Biol, 18:3350-3356.

Garrison W, Jayko M, Bennett W. 1962 Radiation-induced oxidation of protein in aqueous solution. Radiat Res, 16:483-502.

Gavriliouk D, Aitken RJ. 2015. Damage to sperm DNA mediated by reactive oxygen species: Its impact on human reproduction and the health trajectory of offspring. Adv Exp Med Biol, 868:23-47.

Gürler H, Calsici O, Bollwein H. 2015. Inter- and intra-individual variability of total antioxidant capacity of bovine seminal plasma and relationships with sperm  quality before and after cryopreservation. Anim Reprod Sci, 155:99-105.

Gürler H, Malama E, Heppelmann M, Calisici O, Leiding C, Kastelic JP, Bollwein H. 2016. Effects of cryopreservation on sperm viability, synthesis of reactive oxygen species, and DNA damage of bovine sperm. Theriogenology, 86:562-571.

Gutteridge J, Halliwell B. 1990. The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem Sci, 15:129-135.

Halliwell B, Gutteridge JM. 1989. Free Radicals in Biology and Medicine. 2nd Ed. Clarendon Press, Oxford, UK.

Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. 2009. Distinctive chromatin in human sperm packages genes for embryo development. Nature, 460:473-478.

Henle E, Linn S. 1997. Formation, prevention, and repair of DNA damage by iron/hydrogen peroxide. J Biol Chem, 272:19095-19098.

Hunter RH, Rodriguez-Martinez H. 2004. Capacitation of mammalian spermatozoa in vivo, with a specific focus on events in the Fallopian tubes. Mol Reprod Dev, 67:243-250.

Jaroudi S, SenGupta S. 2007. DNA repair in mammalian embryos. Mutat Res Mutat Res, 635:53-77.

Jones R, Mann T, Sherins R. 1979. Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil Steril, 31:531-537.

Krawetz SAS. 2005. Paternal contribution: new insights and future challenges. Nat Rev Genet, 6:633-642.

Lambert IH, Pedersen SF, Poulsen KA. 2006. Activation of PLA2 isoforms by cell swelling and ischaemia/hypoxia. Acta Physiol, 187:75-85.

Lane M, McPherson N, Fullston T. 2014. Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring. PLoS One, 9:e100832.

Liu Y, Fiskum G, Schubert D. 2002. Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem, 80:780-787.

Loschen G, Azzi A, Richter C, Flohé L. 1974. Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett, 42:68-72.

Lundbaek J, Andersen O. 1994. Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers. J Gen Physiol, 104:645-673.

McCarthy MJ, Baumber J, Kass PH, Meyers SA. 2010. Osmotic stress induces oxidative cell damage to rhesus macaque spermatozoa. Biol Reprod, 82:644-651.

MacLeod J. 1943. The role of oxygen in the metabolism and motility of human spermatozoa. Am J Physiol, 138:512-518.

Moazamian R, Polhemus A, Connaughton H, Fraser B, Whiting S, Gharagozloo P, Aitken RJ. 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.

Nichi M, Bols PE, Züge RM, Barnabe VH, Goovaerts IG, Barnabe RC, Cortada CN. 2006. Seasonal variation in semen quality in Bos indicus and Bos taurus bulls raised under tropical conditions. Theriogenology, 66:822-828.

Niki E, Yoshida Y, Saito Y, Noguchi N. 2005. Lipid

peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun, 338:668-676.

Nishikawa T, Tomori Y, Yamashita S, 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 Synaptosome. J Pharm Pharmacol, 41:450-458.

Ochsendorf FR, Fuchs J. 1997. Antioxidants in Germinal Epithelium, Spermatozoa and Seminal Plasma. In. Oxidative Stress in Male Infertility St. Augustin, Germany: Gardez Verlag, pp.85-129

Ollero M, Gil-Guzman E, Lopez MC, Sharma RK, Agarwal A, Larson K, Evenson D, Thomas AJ Jr, Alvarez JG. 2001. Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Hum Reprod, 16:1912-1921.

Noblanc A, Damon-Soubeyrand C, Karrich B, Henry-Berger J, Cadet R, Saez F, Guiton R, Janny L, Pons-Rejraji H, Alvarez JG, Drevet JR, Kocer A. 2013. DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected? Free Radic Biol Med, 65:719-723.

Pérez-Cerezales S, Martínez-Páramo S, Beirão J, Herráez MP. 2010. Fertilization capacity with rainbow trout DNA-damaged sperm and embryo developmental success. Reproduction, 139:989-997.

Rahman MB, Vandaele L, Rijsselaere T, Zhandi M, Maes D, Shamsuddin M, Van Soom A. 2012. Oocyte quality determines bovine embryo development after fertilisation with hydrogen peroxide-stressed spermatozoa. Fertil Dev, 24:608-618.

Richter C, Park J, Ames B. 1988. Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A, 85:6465-6467.

Samans B, Yang Y, Krebs S, Sarode GV, Blum H, Reichenbach M, Wolf E, Steger K, Dansranjavin T, Schagdarsurengin U. 2014. Uniformity of nucleosome preservation pattern in mammalian sperm and its connection to repetitive DNA elements. Dev Cell, 30:23-35.

Schuessler H, Schilling K. 1984. Oxygen effect in the radiolysis of proteins: Part 2 bovine serum albumin. Int J Radiat Biol Relat Stud Physics Chem Med, 45:267-281.

Shalgi R, Magnus A, Jones R, Phillips DM. 1994. Fate of sperm organelles during early embryogenesis in the rat. Mol Reprod Dev, 37:264-271.

Silva PFN, Gadella BM, Colenbrander B, Roelen BAJ. 2007. Exposure of bovine sperm to pro-oxidants impairs the developmental competence of the embryo after the first cleavage. Theriogenology, 67:609-619.

Smith T, Dun M, Smith N, Curry BJ, H.S. C, Aitken RJ. 2013. The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1. J Cell Sci, 126:1488-1497.

St John J, Sakkas D, Dimitriadi K, Barnes A, Maclin V, Ramey J, Barratt C, De Jonge C. 2000. Failure of elimination of paternal mitochondrial DNA in abnormal embryos. Lancet, 355:200.

Sengoku K, Tamate K, Yoshida T, Takaoka Y, Miyamoto T, Ishikawa M. 1998. Effects of low concentrations of nitric oxide on the zona pellucida binding ability of human spermatozoa. Fertil Steril, 69:522-527.

Sies H. 1993. Strategies of Antioxidant Defense. EUr J Biochem, 215: 213-219.

Simões R, Feitosa WB, Siqueira AF, Nichi M, Paula-Lopes FF, Marques MG, Peres MA, Barnabe VH, Visintin JA, Assumpção ME. 2013. Influence of bovine sperm DNA fragmentation and oxidative stress on early embryo in vitro development outcome. Reproduction, 146:433-441.

Stadtman E, Levine R. 2000. Protein oxidation. Ann N Y Acad Sci, 899:191-208.

Storey B. 1997. Biochemistry of the induction and prevention of lipoperoxidative damage in human spermatozoa. Mol Hum Reprod, 3:203-213.

Stradaioli G, Noro T, Sylla L, Monaci M. 2007. Decrease in glutathione (GSH) content in bovine sperm after cryopreservation: comparison between two extenders. Theriogenology, 67:1249-1255.

Tosic J, Walton A. 1946. Formation of hydrogen peroxide by spermatozoa and its inhibitory effect of respiration. Nature, 158:485

Tvrda E, Knazicka Z, Lukac N. 2012. Selected heavy metals versus antioxidant parameters in bull seminal plasma - a comparative study. J Environ Sci Health A Tox Hazard Subst Environ Eng, 47:1261-1266.

Vince S, Žura Žaja I, Samardžija M, Majić Balić I, Vilić M, Đuričić D, Valpotić H, Marković F, Milinković-Tur S. 2018. Age-related differences of semen quality, seminal plasma, and spermatozoa antioxidative and oxidative stress variables in bulls during cold and warm periods of the year. Animal, 12:559-568.

Wathes DC, Abayasekara DR, Aitken RJ. 2007. Polyunsaturated fatty acids in male and female reproduction. Biol Reprod, 77:190-201.

Wood ML, Dizdaroglu M, Gajewski E, Essigmann JM. 1990. Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry, 29:7024-7032.

Zini A, De Lamirande E, Gagnon C. 1995. Low levels of nitric oxide promote human sperm capacitation in vitro. J Androl, 16:424-431.

5b8e872f0e88252835dd6775 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections