THE ROLE OF METAL IONS IN MALEREPRODUCTIONByFalana Benedict AbiolaB.Sc.(Hons), Ilorin 2002; M.Sc. Ile-Ife 2009Matric Number: 109091016Department of Anatomy, College ofMedicine of the University of Lagos.Nigeria.Practice Seminar II
OUTLINEIntroductionTransport/storage problemsMechanism of membrane transportClassificationBioavailability of ionsLiterature reviewConclusionReferences
INTRODUCTIONA metal atom that has either lostor gained an electronA metal ion is thus a metal atomwith a charge.
INTRODUCTIONExert a wide variety of adverseeffects on reproduction anddevelopment( Apostoli and Catalini 2011).
INTRODUCTION Metalloenzymeshydrolytic enzymescatalyze addition or removal of water in asubstratee.g. carbonic anhydrase catalyzes CO2 + H2O →H2CO3redox enzymescatalyze oxidation/reduction of substratee.g. oxidation of hydrocarbons to alcohol by cyt-P450 (Fe-porphyin)e.g. nitrogenase: reduces N2 to NH3 (6 electron
INTRODUCTIONSpecific Metal Ions.Calcium - ZincChromium -PhosphorusPotassium -ManganeseSelenium - Other heavy metals like Cd, Pb
ION TRANSPORTCapture of Trace Ions from the EnvironmentControl of Concentration is essential for lifeBulk ions present in high concentrationTrace ions must be actively accumulatedSelectivity of Ion Uptake is EssentialToxic ions must be excludedBeneficial ions must be accumulated
ION TRANSPORTCharged Ions must pass through aHydrophobic MembraneNeutral gases (O2, CO2) and low chargedensity ions (anions) can move directlythrough the membraneHigh charge density cations require helpOnce
MECHANISMS FOR MEMBRANETRANSPORTIonophores: special carrier molecules thatwrap around metal ions so they can passthrough the membrane by diffusion.Ion Channels: large, membrane-spanningmolecule that form a hydrophilic path fordiffusionIon Pumps: molecules using energy totransport ions in one direction through amembrane
MECHANISMS FOR MEMBRANETRANSPORTPassive Transport: moves ions down theconcentration gradient, requiring no energysourceActive Transport: moves ions against theconcentration gradient, requiring energy fromATP hydrolysis
CLASSIFICATION OF MINERALSMacro or MajormineralsSodium,potassium,magnesium,calcium,phosphorus,sulfur,chloride. Micro or Traceminerals (bodyneeds relativelyless)Chromium,manganese, iron,cobalt,molybdenum,copper, zinc,fluoride, iodine,selenium,silicon, tin,arsenic, nickel.
CALCIUM Developing and maintaininghealthy bones and teeth, Blood clotting, musclecontraction and nervetransmission, oxygen transport,cellular secretion of fluids andenzyme activity, optimal intakehelps reduce the risk ofosteoporosis.
CHROMIUMAids in glucose metabolismPotentiates insulin and serves as acomponent of glucose tolerancefactor.
SELENIUM Component of glutathione peroxidasecatalyzes removal of hydrogen peroxide Component of iodothyronine-5’- deiodinaseConverts T4 to T3 Improves killing ability of neutrophilsGSH = reduced glutathioneGSSG = oxidized glutathioneGSH + H2O2 GSSG + H2O
PHOSPHORUSWorks with calcium to develop andmaintain strong bones and teeth Enhances use of other nutrients Plays a key role in cell membraneintegrity and intercellularcommunication critical for properenergy processing in the body.
MANGANESEKey component of enzymesystem including oxygen handlingenzymes, supports brain functionand reproduction.Required for blood sugarformation and part of bonestructure.
MINERALSMineral Contaminate body partaffectedProtective nutrientAluminum Stomach bone brain Possibly magnesiumArsenic Cells (cellular metabolism) Selenium, iodine, calciumzinc, vitamin C, sulphuramino acids)Cadmium Renal cortex of the kidney,Heart, blood vessels to thebrain appetite and smellcentre, every known processin the development ofCancerZinc, Calcium, Vitamin CSulphur ammo acidsLead Bone, Liver, Kidney,Testes,Pancreas Heart,Brain, Nervous systemZinc, Iron Calcium, VitamC, Vitamin E, Sulphur,Amino acidsMercury Nervous system, appetiteand pain centre of the brain,Immune system CellmembranesREFERENCE: NFM 38,NFM Nutrition ScienceNews; December 2005
NON ESSENTIAL MINERALSHumans are exposed toenvironmentally andoccupationally to metal aerosolsincluding lead and cadmium (Benoffet al., 2000;Akinloye et al 2006 ).These toxicant accumulate inmale reproductive organs (Benoff etal., 2000).
CA+ AND K+ CHANELLSMultiple Ca2+ and K+ Channelshave been identified in human testesand spermatozoa These channels are involved in earlyevents of acrosome reactions, thesechannels offer entry paths for metallictoxicants into mature spermatozoa.(Benoff et al., 2000)
WHY ARE CERTAIN METAL IONSINVOLVED?A. Rule of Abundancewhen a process can be accomplished usingany of several metal ions, then the moleculewill “pick” the most abundant ione.g. Ca+2and Sr+2carbonate/phosphatecompounds equally insoluble. Why aren’tbones made from Sr? (Ca is much moreabundant)e.g. Zn enzymes can use Co+2effectively, but“chose” Zn because it is much more abundant
WHY ARE CERTAIN METAL IONSINVOLVED?B. Rule of Efficiencyan organism will utilize the most efficient ion iftwo are in equal abundancee.g. two electron carriers:flavodoxins (-0.185V potential) with no metalionferridoxins (-0.420V) Fe-S metalloenzymeboth are similar in function, but the ferridoxins aremuch more efficient and powerful than theflavodoxins and are therefore employed more
WHY ARE CERTAIN METAL IONSINVOLVED?C. Rule of Basic Fitness (MostImportant!)no matter how abundant an ionis, if it can’t do the job it isn’tgoing to be used.the ion has to function in anaqueous solution at neutral pHand ~25oC, so most “jobs” canonly be performed by a limitednumber of ions.
LITERATURE REVIEWMetal ions act as matchmakersfor proteins. Yi Lu ( 2009).Match makers for single domainproteins. Salgado et al (2010).
METAL IONS ANDREPRODUCTIONMercury intoxication has beenassociated with male reproductivetoxicity in the experimentalanimals.( Rao and Sharma 2001).
METAL IONS AND REPRODUCTIONSelenium and zinc administrationwas reported to attenuate leadreproductive toxicity in male SD-rats ( Falana and Oyeyipo 2012)
METAL IONS ANDREPRODUCTIONMercury may induce oxidativedamages in rat tissues asevidenced by increase in MDAlevels and depleted GSHcontent. (Sener et al., 2003)
METAL IONS ANDREPRODUCTIONMercury produces asignificant reduction inepididymal sperm viabilityand motility in murines (Rao and Sharma 2001)
METAL IONS AND REPRODUCTIONZinc is an essential trace elementfor spermatogenesis (Yamaguchi etal., 2009)Co administration of zinc withfolic acid has been shown to boostpenile enlargement. (Yamaguchi etal., 2009)
METAL IONS ANDREPRODUCTION Zinc plays an important role in DNA replication,transcription and protein synthesis influencing celldivision and differentiation (Anderson and Desmic 1999) Zinc is a critical element in male reproductive systemfor proper hormonal metabolism, sperm formation andmotility, zinc deficiency has been associated withimpotence and reduced sexual performance (ModupeOgunlesi 2009)
METAL IONS AND REPRODUCTIONOccupational and environmentalexposures to toxic pollutantscontributes significantly todeclining sperm concentrationsand male infertility (Carlsen et al.,1992, Agar et al., 1995,, Adamopoulous et al.,1996, Bcker and berhane 1997)
METAL IONS AND REPRODUCTIONThese study was criticizedbecause it fails to consider thatsperm counts clearly differ bygeographic location (Fisch andGolubuff 1996; Paulsen et al 1996; Carlsen et al., 1992)
METAL IONS AND REPRODUCTIONNonethe less geographicvariations in semen quality (Fisch andGoluboff 1996; becker and Behane 1997) may stillbe inluencd by environmentalfactors ( Fisch and Goluboff 1996) whichexhibit considerable variationbetween climatic seasons (Sram et al1996)
METAL IONS AND REPRODUCTIONMore importantly, environmentalfactors differ between areas ( Fribergand Vahter 1983., Svenson et al 1987; Buchancova et al.,1994; Sram et al.,1996) with higher amountof pollutants closer to sources ofindustrialisation (Benin et al., 1999)
METAL IONS AND REPRODUCTIONPb2+ and Cd2+ prefentiallyaccumulate in male reproductiveorgans ( Danielson et al., 1984; Oldereid et al.,1993; jackson et al 1995)An increase in Pb2+ and Cd2+often occur simultaneously ( Stachelet al., 1989)
METAL IONS AND REPRODUCTIONSeveral death pathways will be activatedfollowing lead toxicity .(Kumari et al.,2013)Mitochondrial pathway which involvesthe inhibition of the heme a3-cuBetabinuclear centre of Ccox: an enzymeconcerned with the conversion ofmolecular oxygen into water at complexV of the ETC.
METAL IONS AND REPRODUCTIONPrevious studies have shown thatheavy metals like Mercury,cadmium and lead are capable ofinducing wide range toxicity inthe germinal epithelium (Xiao et al.,2010)
METAL IONS IN REPRODUCTIONMorphometric studies reveals lowcell count, distorted lumen andcell death in general;Other physiological changesinclude male infertility andtumorigenesis (Xiao et al., 2012)
SUMMARY AND CONCLUSIONTerminating the cause(s)Nanoparticles awarenessGovernment policiesOccupational and environmentalproblems revisited.
REFERENCES Apostoli P and Catalini, S (2011). Metal ions Affecting Reproduction andDevelopment. Met ions life sci.8: 263-303 Adamopoulos DA., Pappa A, Nicopoulou, S. et al., (1996). Seminal volumeand total sperm number trends in men attending sub-fertility clinics in thegreater Athens area during the period 1977-1993. Reprod.,9, 1936-1941 Atar D, Backx,PH, Appel MM. et al .,(1995). Excitation-Transcriptioncoupling mediated by zinc influx through voltage-dependent calciumchanels.J.Biol.Chem, 270,2473-2477 Becker, S. and Berhane, K (1997) A met-analysis of 61 sperm count studiesrevisited. Fertil.steril., 67,1103-1108 Bennof, S, Jabbob, A and Hurley, R (2000).Male fertility and environmentalexposure to lead and cadmium. Human reproduction update (6) 2:107-121 Jenny.P. glusker, Amy K. Kats and Charles W. Bock (1999).Metal ions inbiological system .The Rigaku Journal 16(2):1-10
REFERENCES Benin AL, Sargent JD., DaltonM, et al., (1999).High Concentrations ofHeavy metals in Neighborhoods near Ore smelters in NorthernMexico.Environ.Health Perspect.,107,279-284 Buchancova, J.,Knizkova, M.,Hyllova, D.et al (1994) Content of selectedtrace elements (Al, As,Cd,Cu,Fe,Hg,Mn,Ni,Pb,Zn) in blood urine, hair ofblood donors without occupational exposure to theses metals.CentEur.J.Public health,2,82-87 Carlsen, E.,Giwercman, A.,Keiding,Net al (1992). Evidence for decreasingquality of semen during the past 50 years.Br.Med.J.305, 609-613 Falana, B.A and Oyeyipo, I.P (2012). Selenium and Zinc Attenuate Lead-induced reroductive toxicity in male Sprague-Dawley Rats. ResearchJournal of Medical Sciences 6(2):66-70 Fisch, H and Goluboff E.T (1996).Geographic Variations in Sperm Counts:A Potential Cause o Bias in Studies of Semen Quality. Fertil.Steril.65,1044-1046
REFERENCES Fukushima et al., (2005). Effects of Male ReproductiveToxicant on Gene Expression in Rat Testes.J.Toxicol.Sci.30(3):195-206 Hidiroglou M, and Knipfel J.E (1984). Zinc in MammalianSperm: A Review.J.Diary. Sc.i 67:1147-1156 Glusker, JP, Kats AK, and Bock C.W (1999).Metal ions inBiological Systems. The Rigaku Journal 16(2):1-10 Matzui MM, and Lamb DJ. Genetic Dissection of MammalianFertility Pathways.Nat.med 8 suppl:533-540 Markku Saaranen (1990). Glutathione Peroxidase and SomeMetal ions in Male Reproductive System 69,(5): 453-454 Merker HJ and Gunther T.(1997). Testis Damage Induced byZinc deficiency in Rat. J.Trace element 11:19-22
REFERENCES Miura T, Ando A, Miura C, Yamauchi K .(2002). Comparative StudiesBetween Invivo and Invitro Spermatogenesis of Japanesse Eel(Anguinajaponica). Proc Natl Acad Sci USA 88:5774-5778 Miura T, Higuchi M, Ozaki Y, Ohta ,T and Miura C.(2006) .Progestin is anessential factor for the initiation of meiosis in spermatogenic cell of theeel.Proc. Natl .Acad.Sci .USA 103:7333-7338 Miura T, Yamauchi K, Takahashi H, and Nagahama, Y (1991) HormonalInduction of all the Stages of Spermatogenesis invitro in the Male JapaneseEel (Anguilla japonica) Proc. Natl .Acad .Sci. USA ,88:5774-5778 Morisawa M, and Mohri H. (1972).Heavy Metals and SpermatozoonMotility. I. distribution of iron, zinc, and copper in sea urchin spermatozoa.Exp.Cell.Res.70:311-316 Salgado, E.N et al.,(2010) Metal Templated design of protein interfaces.Proc.Natl. Acad .Sci .USA ,107:1827-1832
REFERENCES Ogunlesi Modupe(2009) Determination of theconcentration of zinc and vitamin c in oyster and somemedicinal plants used to correct male factor fertility.Journal of Natural Product 2:89-97. Yamamoto et al.,(2005). Protein expression analysis ofrat testes induced testicular toxicity with severalreproductive toxicants. The Journal of ToxicologicalSciences 30(2):111-126 Yi Lu (2009). Metal ions as matchmakers for protein.Current Issue 107(5):234-239. Xiao X, Mruk DD, Cheng FL, Cheng CY (2012). C-Srcand C-Yes are two unlikely partners ofspermatogenesis and their roles in blood-testes barrierdynamics. Adv Exp Med Biol. 763: 295-317.
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