Download - Role of metal ions
THE ROLE OF METAL IONS IN MALE REPRODUCTION
By Falana Benedict Abiola B.Sc.(Hons), Ilorin 2002; M.Sc. Ile-Ife 2009
Matric Number: 109091016 Department of Anatomy, College of
Medicine of the University of Lagos. Nigeria. Practice Seminar II
OUTLINEIntroductionTransport/storage problemsMechanism of membrane transportClassificationBioavailability of ionsLiterature review ConclusionReferences
INTRODUCTION
A metal atom that has either lost or gained an electron
A metal ion is thus a metal atom with a charge.
INTRODUCTION
Exert a wide variety of adverse effects on reproduction and development( Apostoli and Catalini 2011).
INTRODUCTION Metalloenzymes
hydrolytic enzymescatalyze addition or removal of water in a
substratee.g. carbonic anhydrase catalyzes CO2 + H2O →
H2CO3
redox 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
transformation)
INTRODUCTIONSpecific Metal Ions.
Calcium - ZincChromium -PhosphorusPotassium -ManganeseSelenium - Other heavy metals like Cd, Pb
Part of the male reproductive tract .
Pastor-Soler N et al. Physiology 2005;20:417-428
©2005 by American Physiological Society
ION TRANSPORT
Capture of Trace Ions from the EnvironmentControl of Concentration is essential for lifeBulk ions present in high concentrationTrace ions must be actively accumulated
Selectivity of Ion Uptake is EssentialToxic ions must be excludedBeneficial ions must be accumulated
ION TRANSPORTCharged Ions must pass through a
Hydrophobic MembraneNeutral gases (O2, CO2) and low charge
density ions (anions) can move directly through the membrane
High charge density cations require helpOnce
MECHANISMS FOR MEMBRANE TRANSPORT
Ionophores: special carrier molecules that wrap around metal ions so they can pass through the membrane by diffusion.
Ion Channels: large, membrane-spanning molecule that form a hydrophilic path for diffusion
Ion Pumps: molecules using energy to transport ions in one direction through a membrane
MECHANISMS FOR MEMBRANE TRANSPORT
Passive Transport: moves ions down the concentration gradient, requiring no energy source
Active Transport: moves ions against the concentration gradient, requiring energy from ATP hydrolysis
CLASSIFICATION OF MINERALS
Macro or Major mineralsSodium,
potassium, magnesium, calcium, phosphorus, sulfur, chloride.
Micro or Trace minerals (body needs relatively less)Chromium,
manganese, iron, cobalt, molybdenum, copper, zinc, fluoride, iodine, selenium, silicon, tin, arsenic, nickel.
CALCIUM Developing and maintaining healthy bones and teeth,
Blood clotting, muscle contraction and nerve transmission, oxygen transport, cellular secretion of fluids and enzyme activity, optimal intake helps reduce the risk of osteoporosis.
CHROMIUM
Aids in glucose metabolism
Potentiates insulin and serves as a component of glucose tolerance factor.
POTASSIUM
Regulates heartbeat
maintains fluid balance
helps muscle contract.
SELENIUM
Component of glutathione peroxidasecatalyzes removal of hydrogen peroxide
Component of iodothyronine-5’- deiodinase Converts T4 to T3
Improves killing ability of neutrophils
GSH = reduced glutathioneGSSG = oxidized glutathione
GSH + H2O2 GSSG + H2O
PHOSPHORUS
Works with calcium to develop and maintain strong bones and teeth
Enhances use of other nutrients Plays a key role in cell membrane
integrity and intercellular communication critical for proper energy processing in the body.
MANGANESE
Key component of enzyme system including oxygen handling enzymes, supports brain function and reproduction.
Required for blood sugar formation and part of bone structure.
MINERALSEssential minerals Essential trace and
mineralsNon essential contaminant minerals
Calcium Chromium Aluminum
Chloride Copper Arsenic (in abundance)
Magnesium Cobalt Barium
Phosphorus Fluorine Beryllium
Potassium Iodine Cadmium
Sodium Iron Lead
Sulphur Manganese Lithium
Molybdenum Mercury
Selenium Rubidium
Vanadium Strontium
Zinc REFERENCE: NFM 38, NFM Nutrition Science News; December 2005
EFFECTS OF NON ESSENTIAL MINERALSMineral Contaminate body part
affectedProtective nutrient
Aluminum Stomach bone brain Possibly magnesium
Arsenic Cells (cellular metabolism)
Selenium, iodine, calcium, zinc, vitamin C, sulphur amino acids)
Cadmium Renal cortex of the kidney, Heart, blood vessels to the brain appetite and smell centre, every known process in the development of Cancer
Zinc, Calcium, Vitamin C, Sulphur ammo acids
Lead Bone, Liver, Kidney, Testes,Pancreas Heart, Brain, Nervous system
Zinc, Iron Calcium, Vitamin C, Vitamin E, Sulphur, Amino acids
Mercury Nervous system, appetite and pain centre of the brain, Immune system Cell membranes
REFERENCE: NFM 38, NFM Nutrition Science News; December 2005
NON ESSENTIAL MINERALS
Humans are exposed to environmentally and occupationally to metal aerosols including lead and cadmium (Benoff
et al., 2000; Akinloye et al 2006 ).
These toxicant accumulate in male reproductive organs (Benoff et al., 2000).
CA+ AND K+ CHANELLS
Multiple Ca2+ and K+ Channels have been identified in human testes and spermatozoa
These channels are involved in early events of acrosome reactions, these channels offer entry paths for metallic toxicants into mature spermatozoa. (Benoff et al., 2000)
REPRODUCTIVETOXICANTS
2,5 hexanedione ( Sertoli cell toxicant),
Ethylene glycol monomethyl ether EGME; (Spermatocytes toxicant),
Cyclophosphamide(Spermatogoonia toxicant), and
Sulphalazin. Fukushima et al., (2005)
BIOAVAILABILITYBioavailability
Influenced by genetics, aging, nutritional status & other food compounds
AbsorptionSmall intestine & large intestine
RegulationKidneys & small intestine
BIOAVAILABILITY
WHY ARE CERTAIN METAL IONS INVOLVED?
A. Rule of Abundancewhen a process can be accomplished using
any of several metal ions, then the molecule will “pick” the most abundant ione.g. Ca+2 and Sr+2 carbonate/phosphate compounds equally insoluble. Why aren’t bones made from Sr? (Ca is much more abundant)
e.g. Zn enzymes can use Co+2 effectively, but “chose” Zn because it is much more abundant
WHY ARE CERTAIN METAL IONS INVOLVED?B. Rule of Efficiency
an organism will utilize the most efficient ion if two are in equal abundancee.g. two electron carriers:flavodoxins (-0.185V potential) with no metal
ionferridoxins (-0.420V) Fe-S metalloenzyme
both are similar in function, but the ferridoxins are much more efficient and powerful than the flavodoxins and are therefore employed more
WHY ARE CERTAIN METAL IONS INVOLVED?
C. Rule of Basic Fitness (Most Important!)no matter how abundant an ion
is, if it can’t do the job it isn’t going to be used.
the ion has to function in an aqueous solution at neutral pH and ~25oC, so most “jobs” can only be performed by a limited number of ions.
LITERATURE REVIEW
Metal ions act as matchmakers for proteins. Yi Lu ( 2009).
Match makers for single domain proteins. Salgado et al (2010).
METAL IONS AND REPRODUCTION
Mercury intoxication has been associated with male reproductive toxicity in the experimental animals.
( Rao and Sharma 2001).
METAL IONS AND REPRODUCTION
Selenium and zinc administration was reported to attenuate lead reproductive toxicity in male SD-rats ( Falana and Oyeyipo 2012)
METAL IONS AND REPRODUCTION
Mercury may induce oxidative damages in rat tissues as evidenced by increase in MDA levels and depleted GSH content. (Sener et al., 2003)
METAL IONS AND REPRODUCTION
Mercury produces a significant reduction in epididymal sperm viability and motility in murines
(Rao and Sharma 2001)
METAL IONS AND REPRODUCTION
Zinc is an essential trace element for spermatogenesis (Yamaguchi et al., 2009)
Co administration of zinc with folic acid has been shown to boost penile enlargement. (Yamaguchi et al., 2009)
METAL IONS AND REPRODUCTION Zinc plays an important role in DNA replication,
transcription and protein synthesis influencing cell division and differentiation (Anderson and Desmic 1999)
Zinc is a critical element in male reproductive system for proper hormonal metabolism, sperm formation and motility, zinc deficiency has been associated with impotence and reduced sexual performance (Modupe Ogunlesi 2009)
METAL IONS AND REPRODUCTION
Occupational and environmental exposures to toxic pollutants contributes significantly to declining sperm concentrations and male infertility (Carlsen et al., 1992, Agar et al., 1995,, Adamopoulous et al., 1996, Bcker and berhane 1997)
METAL IONS AND REPRODUCTION
These study was criticized because it fails to consider that sperm counts clearly differ by geographic location (Fisch and
Golubuff 1996; Paulsen et al 1996; Carlsen et al., 1992)
METAL IONS AND REPRODUCTION
Nonethe less geographic variations in semen quality (Fisch and
Goluboff 1996; becker and Behane 1997) may still be inluencd by environmental factors ( Fisch and Goluboff 1996) which exhibit considerable variation between climatic seasons (Sram et al 1996)
METAL IONS AND REPRODUCTION
More importantly, environmental factors differ between areas ( Friberg and Vahter 1983., Svenson et al 1987; Buchancova et al.,
1994; Sram et al.,1996) with higher amount of pollutants closer to sources of industrialisation (Benin et al., 1999)
METAL IONS AND REPRODUCTION
Pb2+ and Cd2+ prefentially accumulate in male reproductive organs ( Danielson et al., 1984; Oldereid et al., 1993; jackson et al 1995)
An increase in Pb2+ and Cd2+ often occur simultaneously ( Stachel et al., 1989)
METAL IONS AND REPRODUCTION
Several death pathways will be activated following lead toxicity .(Kumari et al.,2013)
Mitochondrial pathway which involves the inhibition of the heme a3-cuBeta binuclear centre of Ccox: an enzyme concerned with the conversion of molecular oxygen into water at complex V of the ETC.
METAL IONS AND REPRODUCTION
Previous studies have shown that heavy metals like Mercury, cadmium and lead are capable of inducing wide range toxicity in the germinal epithelium (Xiao et al., 2010)
METAL IONS IN REPRODUCTION
Morphometric studies reveals low cell count, distorted lumen and cell death in general;
Other physiological changes include male infertility and tumorigenesis (Xiao et al., 2012)
SUMMARY AND CONCLUSION
Terminating the cause(s)Nanoparticles awarenessGovernment policiesOccupational and environmental
problems revisited.
THANKS
Thanks for listening.
REFERENCES Apostoli P and Catalini, S (2011). Metal ions Affecting Reproduction and
Development. Met ions life sci.8: 263-303 Adamopoulos DA., Pappa A, Nicopoulou, S. et al., (1996). Seminal volume
and total sperm number trends in men attending sub-fertility clinics in the greater Athens area during the period 1977-1993. Reprod.,9, 1936-1941
Atar D, Backx,PH, Appel MM. et al .,(1995). Excitation-Transcription coupling mediated by zinc influx through voltage-dependent calcium chanels.J.Biol.Chem, 270,2473-2477
Becker, S. and Berhane, K (1997) A met-analysis of 61 sperm count studies revisited. Fertil.steril., 67,1103-1108
Bennof, S, Jabbob, A and Hurley, R (2000).Male fertility and environmental exposure to lead and cadmium. Human reproduction update (6) 2:107-121
Jenny.P. glusker, Amy K. Kats and Charles W. Bock (1999).Metal ions in biological system .The Rigaku Journal 16(2):1-10
REFERENCES Benin AL, Sargent JD., DaltonM, et al., (1999).High Concentrations of
Heavy metals in Neighborhoods near Ore smelters in Northern Mexico.Environ.Health Perspect.,107,279-284
Buchancova, J.,Knizkova, M.,Hyllova, D.et al (1994) Content of selected trace elements (Al, As,Cd,Cu,Fe,Hg,Mn,Ni,Pb,Zn) in blood urine, hair of blood donors without occupational exposure to theses metals.Cent Eur.J.Public health,2,82-87
Carlsen, E.,Giwercman, A.,Keiding,Net al (1992). Evidence for decreasing quality 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. Research Journal 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 Reproductive Toxicant on Gene Expression in Rat Testes.J.Toxicol.Sci. 30(3):195-206
Hidiroglou M, and Knipfel J.E (1984). Zinc in Mammalian Sperm: A Review.J.Diary. Sc.i 67:1147-1156
Glusker, JP, Kats AK, and Bock C.W (1999).Metal ions in Biological Systems. The Rigaku Journal 16(2):1-10
Matzui MM, and Lamb DJ. Genetic Dissection of Mammalian Fertility Pathways.Nat.med 8 suppl:533-540
Markku Saaranen (1990). Glutathione Peroxidase and Some Metal ions in Male Reproductive System 69,(5): 453-454
Merker HJ and Gunther T.(1997). Testis Damage Induced by Zinc deficiency in Rat. J.Trace element 11:19-22
REFERENCES Miura T, Ando A, Miura C, Yamauchi K .(2002). Comparative Studies
Between Invivo and Invitro Spermatogenesis of Japanesse Eel(Anguina japonica). Proc Natl Acad Sci USA 88:5774-5778
Miura T, Higuchi M, Ozaki Y, Ohta ,T and Miura C.(2006) .Progestin is an essential factor for the initiation of meiosis in spermatogenic cell of the eel.Proc. Natl .Acad.Sci .USA 103:7333-7338
Miura T, Yamauchi K, Takahashi H, and Nagahama, Y (1991) Hormonal Induction of all the Stages of Spermatogenesis invitro in the Male Japanese Eel (Anguilla japonica) Proc. Natl .Acad .Sci. USA ,88:5774-5778
Morisawa M, and Mohri H. (1972).Heavy Metals and Spermatozoon Motility. 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 the concentration of zinc and vitamin c in oyster and some medicinal plants used to correct male factor fertility. Journal of Natural Product 2:89-97.
Yamamoto et al.,(2005). Protein expression analysis of rat testes induced testicular toxicity with several reproductive toxicants. The Journal of Toxicological Sciences 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-Src and C-Yes are two unlikely partners of spermatogenesis and their roles in blood-testes barrier dynamics. Adv Exp Med Biol. 763: 295-317.