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Indian Journalof ExperimentalBiology Vol. 43. November2005.pp 963-974
ReviewArticle
Mechanism,measurement, andpreventionof oxidative stress in male reproductivephysiology Ashok Agarwal* & Sushil A Prabakaran Centerfor AdvancedResearchin HumanReproduction,Infertility, and SexualFunction,GlickmanUrological Institute,and Departmentof ObstetricsandGynecology,The ClevelandClinic Foundation,9500EuelidAvenue,Desk A19.I, Cleveland, Ohio, 44195,USA Numerousfactors influence male fertility. Among thesefactors is oxidative stress(OS), wmcb bas elicited an enormous interest in researchersin recent period. Reactiveoxygen species(ROS) are continuouslyproducedby various metabolic and physiologicprocesses.OS occurswhen the delicatebalancebetweenthe productionof ROSand the inherentantioxidant capacity of the organism is distorted. Spermatozoaare particularly sensitiveto ROS as their plasma membrane containspolyunsaturatedfatty acids (PUFA), which oxidizes easily.They also lack cytoplasmto generatea robustpreventive and repair mechanismagainstROS. The transition metal ions that are found in the body have a catalytic effect in the generationof ROS. Lifestyle behaviourssuchas smokingand alcohol useand environmentalpollution further enhancethe generationof ROS and thus,causedestructiveeffectson variouscellular organelleslike mitochondria.spermDNA etc. This article analyzesthe detrimentaleffectsof OS on male ferdlity. measurement of OS and effcctive ways to decreaseor eliminatethem completely. We have also provided information on oxidative stressin other systemsof the body, which may be appliedto future researchin the field of reproductivebiology. Keywords: Male fertility. Oxidative stress,Spermatozoa
Introduction As many as 15% of all couples living in the United States have difficulty conceiving a child. Male factors are responsible in at least 30% of the cases, and in another 20%, the pathology is found both in men and women. Approximately 6% of men between the age of 15 and 50 suffer from male infertilityl. A metaanalysis of 61 studies worldwide found a downward trend in sperm count and volume of seminal fluid over the past 50 years2. In 1940, the average sperm count was 113 million per mI. By 1990, the count had dropped to 66 million per mI3. This decreasing trend in sperm count has led to speculation that recent environmental, dietary and/or lifestyle changes are interfering with a man's ability to produce spermatozoa. It is believed that these factors exert dleir detrimental effects through oxidative stress (OS). Oxidative stress (OS) and its significance-OS occurs as a consequence of an imbalance between the production of reactive oxygen species (ROS) and the available antioxidant defense against them4,S.ROS are free radicals and peroxides that are derived from the
metabolismof oxygen and are presentin all aerobic organisms.Theyray a significant role in many biological processes.as can affect the individual molecules and thus the entire organism.as is believed to be one of the major causesof many humandiseases. Some of the OS-mediatedpathologies are listed in Table 1. Virtually every discipline of medicine is interestedin as and its implications.It is believed that the new field of 'Oxidative Stress,Diagnostics and Therapeutics'may have a significant impact on the economics,scienceand the practiceof medicinein the presentcentury7. Table I-Diseases anddegenerativeprocessesmediatedby oxidativestress Alzheimer's disease
Iron overload
Autoimmune disease
Ischemic-reperrusion Rheumatoidarthritis injury Maculardegeneration Segmentalprogeria disorders
Cancer
Cardiovascular Multiple sclerosis .Correspondentauthor disease Phone: (216) 444-9485.Fax: (216) 445-6049; Cataractogenesis Musculardystrophy E-mail:
[email protected]; Pancreatitis Website:www.clevelandclinic.orgjReproductiveResearchCenter Diabetes
Parkinson'sdisease
Aging
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Mechanism of ROS formation Oxygen in the atmosphere has two unpaired electrons, and these unpaired electrons have parallel spins. Oxygen is usually non-reactive to organic molecules that have paired electrons with opposite spins. This oxygen is considered to be in a ground (triplet or inactive) state and is activated to a singlet (active) state by two different mechanisms: a) Absorption of sufficient energy to reverse the spin on one of the unpaired electrons. .0-0.
.0.-0:
Triplet oxygen(rr) (Groundstate)
Singlet oxygen
M. Gandini Let at. GIutadJjcx.:: b~ of dyspermia: Effm on the liPJlJeroxNtMion ~ HRep,oo. 9 (1994) 2044105 TauIx:r P F. Zaneveld L J. ~ng D et at. con..-:.n of human split ej~ 1- Sp:I~ fnM:tI&:. ~ globulins. albumin. lal:lDfelTin. b3R§ferriD aIM! odIa- plasma lXOfeios. J Reprod Feltil. 43 (1975) 249-
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106 Alvarez J G &. StoreyB T, Taurioo,hypotaurioe.epinepbri~ and albumin inhibit lipid peroxidationin rabbit spennaIozoa and protect againstloss of motility, Bioi Reprod,29 (1983) 548. 107 de Lamirande E & GagnonC, Capacitation-associated pr0duction of superoxideanion by human spennatozoa.Free Radic Bioi Med, 18 (1995)487. 108 PeekerR, AbramssonL &. Marklund S L. Superoxidedismutaseisoenzymesin humanseminalplasmaand spermatozoa,Mol Hum Reprod,3 (1997) 1061. 109 Baker H W, Brindle J, Irvine D S et aL, Protectiveeffect of antioxidantson the impairment of sperm motility by activatedpolymorphonuclearleukocytes,Fertil Steril, 65 (1996) 411. 110 Zini A, FischerM A, Mak V et aI., Catalase-likeand superoxide dismutase-likeactivities in human seminal plasma. Ural Res,30 (2002)321. III Sikka S C, Role of oxidative stressand antioxidantsin andrology and assistedreproductivetechnology,J Androl, 25 (2004)5. 112 Wangx. FalconeT, Attaran M et aI., Vitamin C and vitamin E supplementationreduce oxidative stress-inducedembryo toxicity and improve the blastocystdevelopmentmte, Fel1il Steril, 78 (2002) 1272. 113 Burton G W, JoyceA & Ingold K U, First proof that vitamin E is major lipid-soluble, chain-breakingantioxidant in humanblood plasma,Lancet,2 (1982) 327. 114 Agarwal A, Nallella K p, Allamaneni S SetaL, Role of antioxidants in treatmentof male infertility: An overview of the literature,ReprodBiomedOnline, 8 (2004)616. 115 LutsenkoE A, CarcamoJ M & Golde D W, Vitamin C prevents DNA mutation induced by oxidative stress.J Bioi Chem,277 (2002) 16895. 116 Irvine D S, Glutathione as a treatment for male infertility, RevReprod,1 (1996)6.
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