Male infertility


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Male infertility

  1. 1. The focus of attentionToday’s focus
  2. 2. What we know
  3. 3. Fig. 46.8Reproductive Anatomy of the Human Male
  4. 4. The male reproductive system comprises ofa pair of testes that are present in a thin-walled sac called the scrotum. . Atemperature 2-3 degrees lower is ideal forthe production of sperms. Internally, thetestis is lobed. There are 15-20 lobes, eachhaving a network of seminiferous tubulesand the interstitial cells between thetubules.The seminiferous tubules produce sperms that are passed along the tubulesThe sperms are produced by a process called the spermatogenesis. Theinterstitial cells are also called the Leydig cells and they secrete thehormone testosterone.Testes
  5. 5. From the seminiferous tubules, the sperms are passed into anetwork of 10-12 ducts called vasa efferentia. They are thenpassed into a highly coiled tubular part called the epididymis.The sperms from the epididymis pass into a distinct tube calledthe vas deferens, also called the sperm duct. . Vas deferens isjoined by the duct from the seminal vesicle to form theejaculatory duct. The duct then passes through the prostrateglands and opens into the urethra.Duct System
  6. 6. GlandsThe various glands associated with the male reproductive systemare as follows:• Seminal vesicles• Prostrate gland• Cowpers glands• Penis
  7. 7. Seminal Vesicles A pair of seminal vesicles are glands that are present behindthe urinary bladder. Each sperm duct has the seminal vesicle of its side secretinga fluid into the common ejaculatory duct. This fluid along with the sperms iscalled the semen, a milky fluid.Prostate Gland It is a bi-lobed gland near the opening of the urethra. Theprostate gland also pours its secretion into the urethra.Cowpers Glands They are a pair of small ovoid glands that secrete lubricatingfluid into the urethra just before it enters the penis.Penis: Penis is a muscular organ containing erectile tissue. The tissue is richlysupplied with blood vessels.Glands
  8. 8. ProductionOf Sperm - Spermatogenesis
  9. 9. Fig. 46.11Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
  10. 10. Sperm
  11. 11. Sperm55-65 µm in lengthThree parts head, neck and tail. On the outside of the anterior twothirds of the head is a thick cap called the acrosome that is formedmainly from the Golgi apparatus.It contains enzymes similar to those found in lysosomeshyaluronidase and powerful proteolytic enzymes. These playimportant roles in allowing the sperm to enter the ovum and fertilizeit.
  12. 12. SpermThe tail of the sperm, called the flagellum, has threemajor components:(1) A central skeleton constructed of 11 microtubules, collectivelycalled the Axoneme(2) A thin cell membrane covering the Axoneme(3) A collection of mitochondria surrounding the axoneme in theproximal portion of the tail (called the body of the tail)Normal sperm move in a fluid medium at a velocityof 1 to 4 mm/min.
  13. 13. Regulation of Sex Hormone Secretionand Sperm ProductionThis process begins duringpubertyGonadotropin releasinghormone (GnRH) from thehypothalamus stimulates theproduction of the follicle-stimulating hormone (FHS)and luteinizing hormone (LH)from the anterior pituitary.Testes respond to FSH byinitializing spermatogenesis.LH assists spermatogenesisand production of testosterone.Inhibin hormone controlsproduction of sperm count
  14. 14. Male infertilityMale infertility of unknown origin is a condition inwhich fertility impairment occurs spontaneouslyor due to an obscure or unknown cause• It includes 2 categories,1. Unexplained male infertility &2. Idiopathic male infertility.• The dividing line between them is semen analysis,which is normal in the unexplained category andabnormal in idiopathic infertility.
  15. 15. Terminologies1.Azoospermia : Absence of Sperm2.Oligozoospermia : Low Sperm Count3.Asthenozoospermia : Sperm with Poor Motility4.Teratozoospermia : Abnormal shape of Sperm
  16. 16. Causes - male infertilityWhen there is structural abnormality in the spermsWhen there is structural abnormality in the spermsWhen there is functional abnormality in the spermsWhen there is functional abnormality in the sperms
  17. 17. Causes - male infertilityWhen Number is < 1m/ejaculateWhen Number is < 1m/ejaculateWhen Progression is < 2/4When Progression is < 2/4When Motility is < 20%When Motility is < 20%When Abnormal forms are> 85%When Abnormal forms are> 85%
  18. 18. Causes - oxidative stressOxidative stress (OS) is the imbalance betweenthe production of reactive oxygen species (ROS)by the spermatozoa and leukocytes & theantioxidant capacity of the seminal plasma.1. The primary source of ROS production in infertilepatients is the immature spermatozoa.2. Oxidative stress can damage the DNA of thespermatozoa & prevent them fertilizing an egg.3. Reactive oxygen species (ROS) includes oxygenions, free radicals and peroxides.
  19. 19. Causes-inadequate progressionGrade 0 is no movementGrade 0 is no movementGrade 2 is slow movement but not straightGrade 2 is slow movement but not straightGrade 1 is sluggish movementGrade 1 is sluggish movementGrade 3 is movement in a straight lineGrade 3 is movement in a straight lineGrade 4 is terrific speed.Grade 4 is terrific speed.
  20. 20. ROS – In MaleInfertility
  21. 21. ROS – In male infertility
  22. 22. Role of ROS in male infertility1. Idiopathic oxidative stress has been linked with male factor infertility as itis known to contribute to defective spermatogenesis leading to male factorinfertility2. Uncontrolled & excessive production of ROS overwhelms the limitedantioxidant defenses in semen resulting in seminal oxidative stress3. Seminal oxidative stress correlates negatively with sperm concentration,motility and function - adversely affecting fusion events required forfertilization.Superoxide anion, hydroxyl radical and hydrogen peroxide are major reactiveoxygen species (ROS) present in seminal plasma.
  23. 23. ROS - Role in male infertilityROS are produced by the spermatozoa (especially damagedspermatozoa) & seminal leucocytes - most notably granulocytes.ROS directly damage spermDNA, compromising thepaternal genomiccontribution to the embryoThis, in turn, reduces the sperm’s motility and ability to fuse with theoocyte.Reports have indicated that high levels of ROS aredetected in semen samples of 25-40% of infertile men& seems to be the leading cause infertility by 2principal mechanisms:ROS damage the spermmembrane by causinglipid peroxidation ofsperm membrane
  24. 24. Bodys defense against ROSTo maintainnormal cellfunctionExcess ROS is continuouslyinactivated by seminal plasmaantioxidantsGlutathioneperoxidaseThe seminal plasma antioxidants block the formation of new ROSor act as scavengers and remove ROS already generatedNatural antioxidant enzyme systems includeCatalaseSuperoxidedismutase
  25. 25. Underlying facts on anti-oxidantsHowever in conditions of oxidative stress, production of ROS overwhelmsantioxidant defence.However in conditions of oxidative stress, production of ROS overwhelmsantioxidant defence.Hence, there is a pressing need for externalantioxidant support!Hence, there is a pressing need for externalantioxidant support!Antioxidants are the most important defence against free radical inducedinfertilityAntioxidants are the most important defence against free radical inducedinfertilityThe several antioxidant strategies produced by the human body protect itselffrom ROS damageThe several antioxidant strategies produced by the human body protect itselffrom ROS damageThis permits normal oxidative metabolism to occur without damaging the cells,while still allowing for normal ROS-mediated cellular responses such asdestruction of infectious pathogens and intracellular signallingThis permits normal oxidative metabolism to occur without damaging the cells,while still allowing for normal ROS-mediated cellular responses such asdestruction of infectious pathogens and intracellular signalling
  26. 26. The need of the dayLevels of ROS within semen can be ↓ byaugmenting the scavenging capacity of seminalplasma, by antioxidant supplement.Antioxidant supplements boost sperm count,morphology and sperm motility and preventDNA damage to spermAntioxidant supplements boost sperm count,morphology and sperm motility and preventDNA damage to spermBut, what can antioxidant do to the problemof male infertility?But, what can antioxidant do to the problemof male infertility?
  27. 27. The therapeuticsupplementation in maleinfertility
  28. 28. Clomiphene – Role in male fertilityClomiphene citrate influences spermatogenesis and alsoimproves semen quality
  29. 29. Antioxidants in the therapy of maleinfertilityBecause ROS have been associated with spermDNA damage, investigators have studied possibleprotective roles of antioxidants in preventing ortreating sperm DNA damage.
  30. 30. Antioxidants in the therapy of maleinfertility82% trials showed an improvement in either sperm quality orpregnancy rate after antioxidant therapy.10 trials examined pregnancy rate and 6 showed a significantimprovement after antioxidant therapy.The use of oral antioxidants in infertile men couldimprove sperm quality and pregnancy rates.
  31. 31. Antioxidants in the therapy of maleinfertilityUbidecarenoneCarotenoids (Lycopene)Omega 3 fatty acidsCarnitine / Levo CarnitineVitamin E & Vitamin CSeleniumGlutathioneN-acetyl cysteineL ArginineTrace Metals like ZincVitamin B12
  32. 32. UbidecarenoneAlso known as Coenzyme Q10, ubiquinone,coenzyme Q, and abbreviated at times toCoQ10 , CoQ, Q10, or QComponent of the electron transport chain andparticipates in aerobic cellular respiration,generating energy as ATP.Unique capacity of this molecule:
  33. 33. Ubidecarenone - Role in male fertilityIn sperm cells, Co Q10 is concentrated in themitochondrial mid-piece, where it is involved inenergy production.It also functions as an antioxidant, preventinglipid peroxidation of sperm membranes.According to studies, Ubidecarenone showssignificant increase in:
  34. 34. Lycopene - Role in male fertilityBright red carotenoid pigment, phytochemical andpowerful antioxidant with a major role in themanagement of idiopathic male infertility.Most efficient oxygen & free radical quencher andprime carotenoid in plasma / other tissuesIt is a component of human redox defencemechanism against free radicalsFound in high concentrations in the testes andseminal plasmaDecreased levels have been demonstrated in mensuffering from infertility.
  35. 35. Lycopene - Role in male fertilityStudies suggest efficacy of lycopene in maleinfertility as it improves.Sperm ConcentrationSperm MotilitySperm Morphology
  36. 36. Mixed caretenoids - Role in malefertilityCarotenoids work synergistically with Se andvitaminEMixed carotenoids, taken with vitamins C and E,may help protect sperm from damage by freeradicals as it improves -Sperm MotilitySperm MorphologySperm Concentration andImproved Fertility rates
  37. 37. Omega-3 fatty acids - Role in malefertilityOmega−3 fatty acids includes eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA).DHA (Docosahexaenoic acid) is essential formale fertility.Omega-3 fatty acids are abundant in the sperm withDHA being abundant in the sperm tail to havesignificant effect in sperm motility.Its deficiency is linked to low sperm count andinfertility.
  38. 38. Omega-3 fatty acids - Role in malefertilityNormal sperm cells contain an arc-like structurecalled the acrosome. Acrosome is critical infertilization because it houses, organizes, andconcentrates a variety of enzymes that spermsuse to penetrate egg.DHA is essential in fusing the building blocks of theacrosome together.Without DHA, this vital structure does not form andsperm cells dont workDHA plays a major role in regulating membranefluidity in sperm + regulation of spermatogenesis
  39. 39. Omega-3 fatty acids - Role in malefertility
  40. 40. Wheat germ oil - Role in male fertilitySource of Vitamin E and primary function is asan AntioxidantIt is a major chain-breaking antioxidant in thesperm membranesProtects the sperm membrane from oxidativedamage and increased levels are associated withlow levels of reactive oxygen species.It scavenges all 3 types of free radicals, viz.Superoxide,Hydrogen peroxide andhydroxyl radicals.
  41. 41. Wheat germ oil - Role in male fertilityVitamin E enhances sperm performanceVitamin E protects spermatozoa from:1. Oxidative damage2. Loss of motility
  42. 42. Calcium ascorbate – Role in male fertilityNatural form of Vitamin C that is a water-solubleROS scavenger with high potency.Readily absorbed in the blood stream than theother forms of calcium.It is a strong antioxidant destroying free radicalsin the body and protects human spermatozoaagainst endogenous oxidative damage byneutralising :1. Hydroxyl2. Superoxide, &3. Hydrogen peroxide radicals
  43. 43. Calcium ascorbate – Role in male fertilityVitamin C Prevents sperm agglutination.Vitamins C and E act synergistically to protectagainst peroxidative attack on spermatozoa.
  44. 44. Vitamin B 12 - Role in Male FertilityVitamin B12 is important in cellular replication,especially for the synthesis of RNA and DNADeficiency states have been associated withdecreased sperm count and motilityB12 supplementation improves spermparameters such as:1. Sperm concentration,2. Sperm count and3. Sperm motility.
  45. 45. Selenium - Role in Male FertilitySelenium is a nonmetal & a trace mineral that isessential to good health but required only in smallamounts.Its antioxidant properties helps prevent cellulardamage from free radicalsProtects against oxidative sperm DNA damageand is required for:1. Normal testicular development2. Spermatogenesis3. Motility and function
  46. 46. Selenium - Role in Male FertilityEssential for formation of phospholipidhydroperoxide glutathione peroxidase - anenzyme present in spermatids which becomes astructural protein comprising over 50 % of themitochondrial capsule in the mid-piece of maturespermatozoa.Deficiency leads to instability of the mid-piece,resulting in− Defective motility− Breakage of the spermatozoal mid-piece and− Increased morphological abnormalities, mostly affecting thesperm head
  47. 47. Zinc - Role in male fertilityZinc is a trace mineral essential for normalfunctioning of the male reproductive system.Zinc levels are generally lower in infertile menwith diminished sperm countZinc supplementation shows improvement insperm quality, sperm motility, fertilisation capacityand a reduction in the incidence of anti-spermantibodies.
  48. 48. Zinc - Role in male fertilityZinc is found in high concentration in sperm, andis vital in making the outer layer of the sperm, aswell as the tail.Zinc deficiency is associated with decreasedtestosterone levels and sperm countAdministration of exogenous systemic zinc tomales with zinc deficiency can improve spermproduction and sperm motility.Supplementing zinc in the diet can re-establishtestosterone and sperm count levels to acceptablelevels
  49. 49. Zinc - Role in male fertilityZinc therapy results in significant improvement insperm quality with increase in sperm density,progressive motility and improve conception andpregnancy outcome
  50. 50. PiperinePiperine is an alkaloid - a standardized extractfrom the fruits of Piper nigrum L. (black pepper)or Piper longum L. (long pepper)Piperine may be co-administered with variousnutrients for human health.It has antioxidant activityIt lowers lipid peroxidationIt increases the plasma levels of Coenzyme Q10following oral supplementation.
  51. 51. Levocarnitine:Provide energetic substrate for spermatozoa.Sucessful maturation of sperm.Increases spermatozoa per ejaculateIncrease in progressive linear sperm motility inidiopathic asthenospermia.L Arginine:Precursor of nitric oxide, which effectively improves sexualperformance.Effective even in erectile dysfunction casesIncrease sperm count, quality, and fertility