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.

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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.