MALE REPRODUCTIVE SYSTEM

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MALE REPRODUCTIVE SYSTEM
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Objectives

• At the end of the topic, the students should be
  able to
• Explain the functions of the testis
• Discuss spermatogenesis
• Describe the characteristics of a normal sperm
• Explain the role of FSH and inhibin on
  spermatogenesis
• Discuss the contents of semen and its
  abnormalities
• Explain the functions of testosterone
• Explain the control of secretion of
  testosterone 

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Main points in male reproductive physiology

• Importance of Leydig cells and testosterone in
  puberty
• Role of Sertoli cells,testosterone, DHT, and
  estrogen in spermatogenesis
• How testosterone and inhibin functions in the
  adult feedback regulation of the Hypothalamic/
  Pituitary/ Gonadal Axis

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INTRODUCTION

• A pair of testes
• A pair of accessory glands
• Ductal system
• Copulatory organ

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Male reproductive system (Lateral view)
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Male reproductive system (Anterior view)
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Structure of testis
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Seminiferous tubules
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FUNCTIONS

• Production of spermatozoa after puberty for
  fertilization with the ovum from the female
• Coitus process
• Produce androgens

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Testis

• Originates from indifferent gonads during the
  embryonic phase
• Contains lobules (200-300) separated by septum
• Each lobule has 4 seminiferous tubules
• Blood supply is from testicular artery and blood
  drainage is through the Pampiniform plexus into
  the testicular vein
• Seminiferous epithelium contains Sertoli cells
  (Sustentacular cells) and Germ cells
• Leydig cells exist in between tubules
• Produce spermatozoa and androgens
• Divided into two compartments extratubular and
  intratubular

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Histology of the testis
ETC
ITC
Spermatogonia
Leydig cells
SCN
Lumen
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Compartments

• Extratubular vascular and interstitial
  divisions (inclusive of lymphatic channels and
  Leydig cells)
• Intratubular basal and adluminal divisions
  located in the seminiferous tubules

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Spermatogenesis
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Spermatogenesis and spermatozoon structure
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Epididymis
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Blood Testis Barrier

• Formed before spermatogenesis commences
• Formed by Sertoli cells
• Functions
• Stop intratubular spermatozoa from entering
  systemic and lymphatic circulation
• The blood testes barrier is important since
  sperm (with their unique surface antigens) elicit
  an immune response if detected by the immune
  cells in the mans blood, and the antibodies that
  are formed against sperm are designed to
  immobilize and destroy them

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• A number of events can disrupt the blood testes
  barrier and allow the immune system to become
  activated against the sperm.
• These include
• trauma to the testes
• torsion (twisting) of the testes
• a history of a vasectomy and reversal
• any other surgery within the scrotum
• infection within the testes

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Allergic orchitis
Inflammation of the testis due to antisperm
antibodies
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• Ensure the intratubular chemical composition is
  different from the intertubular chemical
  composition (blood, interstitial fluid and lymph)
• As spermatogenesis must occur in a controlled
  microenvironment, any changes in the chemical
  composition will affect normal spermatogenesis

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Functions of Sertoli cells

• Sertoli cells are joined by tight junctions that
  provides barrier to chemicals (Blood testis
  barrier)
• Nourish developing sperm
• Secrete luminal fluid including androgen binding
  proteins (ABP)
• Phagocytize defective sperm
• Mediate testosterone and FSH effects on
  spermatogenesis
• Secrete inhibin which inhibits FSH secretion
• Influence Leydig cells via paracrine secretions
• Embryonic secretion of Mullerian Inhibiting
  Substance (MIS) that ensures male phenotype

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Sertoli cells

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Spermatogenesis

• Process for formation of spermatozoa
• The seminiferous tubules produce haploid cells
  (n)
• Involves several steps including mitosis and
  meiosis
• Takes about 64 days in human
• Consists of three stages
• Spermacytogenesis formation of spermatid from
  spermatogonia
• Spermiogenesis formation from spermatid to
  spermatozoa
• Spermiation the release of spermatozoa into the
  epididymis

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Spermacytogenesis

• Mitosis stage
• spermatogonia type Ad give rise to a pair of
  spermatogonia type Ad or Ap
• spermatogonia type Ap give rise to a pair of
  spermatognia type Ap or B
• mitosis of the germ cells occurs in the basal
  compartment
• incomplete cytokenesis of committed cells (type
  Ap) results in the cells being linked by
  cytoplasmic bridges until spermatozoa is form
• this linkage results in a synchronous development
  of the cells within a given region of the tubule

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Types of cells

• germ cells - - spermatogonia (types A and B)
• spermatogonia type A - for spermatogenic lineage
  (type A dark (Ad) or A pale (Ap), type Ad are
  true stem cells)
• spermatogonia type B - progenitor cell for
  primary spermatocyte
• primary spermatocyte (46 chromosomes, 4N DNA)
• first meiotic division from these cells result in
  secondary spermatocyte (23 chromosomes, 2N DNA)
• second meiotic division from these cells results
  in spermatids
• spermatids (23 chromosomes, 1N DNA) undergoes
  modifications in many parts and gives rise to
  spermatozoa
• spermatozoa, within the seminiferous tubules (and
  distally) the flagella is not motile

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Spermiogenesis

• spermatid phase spermatids develop into
  spermatozoa in 4 stages
• Golgi phase
• - development of the acrosomal granule from the
  Golgi complex forming the acrosomal vesicle at
  the nascent apex (anterior) of cell
• positioning of centrioles at the nascent base of
  flagella
• initiation of formation of axonemal complex from
  one of the centrioles
• Cap phase
• development of acrosomal cap over nucleus and
  condensation of chromatin
• development of flagellum from axonemal complex
• acrosome contains hydrolases (proteases,
  hyaluronidase, neuramidase, acid phosphatase)
  important in penetration of the oocyte membrane
  during fertilization

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Spermiogenesis

• Acrosome phase - spermatid re-orients so tail
  (flagellum) projects into the lumen of the tubule
  and the acrosome towards the base of the
  epithelium
• further condensation of chromatin
• flattening and elongating of nucleus at the
  anterior of the cell
• movement of cytoplasm to the posterior of cell
• further development of flagellum
• linkage of flagellum to nucleus via the
  connecting piece developed from a centriole
• Maturation phase - residual body of cytoplasm
  shed (cell linkages lost) and the cells released
  by Sertoli cell into lumen of tubule

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Spermiation

• released spermatid moved with fluid via
• peristaltic action of myoid cells transporting
  it to the straight tubule
• sperm cannot move yet
• will develop motility in epididymis

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• 1 germ cell produces 64 spermatozoa
• Process takes 2 months (56 64 days ) to
  complete
• 100 million sperm produced each day
• Not all are normal i.e., abnormal increases
  with alcohol, heat, cigarettes, drugs

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• Temperature sensitivity
• Spermatogenesis is temperature sensitive, optimal
  34o C
• Achieved by the descent of the testes out of the
  abdomen
• Arteries and veins supplying the testes
  intertwine, efficiently exchanging heat (from
  artery to veins) to further cool testes

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Scrotum

• Originates from labioscrotal swellings and
  urethral fold
• Pouch that houses the testes
• Main function is to provide an environment which
  is 1-80F lower than the body temperature and also
  to control testicular temperature
• Testicular temperature needs to be controlled for
  spermatogenesis to occur normally

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Control and regulation of testicular temperature
(1)

• Two muscle system cremaster external and tunica
  dartos
• Cremaster external muscle passes along inguinal
  canal and attaches to tunica vaginalis
• Pulls tunica vaginalis as it contracts when the
  environmental temperature drops
• Tunica dartos muscle attaches to scrotal skin and
  forms a septum separating the scrotum
• - Pulls scrotal skin as it contracts when the
  environmental temperature drops

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Control and Regulation of testicular temperature
(2)

• Pampiniform plexus
• consists of convoluted veins and arteries which
  follow the spermatid cord into the inguinal
  canal. Arterial branch comes from spermatid
  artery and venous part enters the spermatid vein
• - controls temperature by dissipating heat from
  the aortal blood through the convolutions before
  reaching the testis

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• The testes is located in the abdominal cavity
  during the fetal stage
• Only descents into scrotum at 7 months of
  pregnancy
• Sometimes do not descend and when born, two
  conditions may occur i.e., cryptochidism or
  monochidism
• Crypotochidism cryptochids are males with both
  testes in inguinal canal/abdominal cavity
• usually sterile
• may either be hereditary or due to lack of
  hormones
• undescended testes are associated with reduced
  fertility, increased risk of testicular cancer
  and psychological problems when the boy is grown
• undescended testes are also more susceptible to
  testicular torsion, infarction and inguinal
  hernias

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• Monochidism monochids are males with only one
  testis descended into scrotum, the other remained
  in inguinal canal/abdominal cavity
• - usually fertile as one testis still functioning
  normally therefore spermatogenesis is not
  impaired
• Approximately 3 of full-term and 30 of
  premature infant boys are born with at least one
  undescended testis, making monochidism/cryptorchid
  ism the most common birth defect of male
  genitalia
• However, most testes descend by the first year of
  life (the majority within three months), making
  the true incidence of cryptorchidism around 1
  overall.

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Ductal System

• Originates from Wolffian ducts (mesonephric
  kidney)
• Mullerian ducts rudiments in prostate gland
  (prostatic utricle/uterus masculinus)
  non-functional but can grow when there is
  estrogen influence causing prostate cancer
• Mesonephric tubules vasa efferentia
• Mesonephric ducts epididymis, vas deferens and
  seminal vesicles
• Urogenital sinus prostatic, cavernous and
  membranous urethra, prostate glands and
  Bulbo-urethral gland (Cowpers gland)
• Rete testis in the testis efferentia ducts and
  then becomes epididymis and vas deferens

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Epididymis

• Originates from mesonephric ducts
• Divided into caput (head), corpus (body) and
  cauda (tail)
• Extra fluid from sperm is reabsorbed to
  concentrate spermatozoa 100X
• Presence of high concentrations of testosterone/
  DHT in the tubule causes epididymis to secrete a
  motility- inducing protein that binds to the cell
  membrane of sperm cells
• Secrete mucoproteins/glycoproteins that coats the
  head of the sperm
• Also secretes carnitine, glycerolphosphorycholine,
  fructose and glycoproteins
• Transit time for spermatozoa to attain maturation
  and the ability to move/motility is about 6 12
  days
• Spermatozoa can move forward and has the ability
  to fertilize ovum once has entered cauda
  epididymis
• Morphological and biochemical changes also occur

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Caput
Corpus
Cauda
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Vas deferens

• Developed from Wolffian ducts
• Vas deferens have a lot of muscle layers (inner
  and outer longitudinal muscle layer with circular
  layers in between this muscles layers are
  important for sperm motility
• Vas deferens form the ampulla near the bladder
• Sperm enters vas deferens from epididymis
• Acts as a reservoir to store spermatozoa
• Also acts as a conduit between testes and urethra
• Mature sperm stored in the Vas Deferens and can
  remain viable for up to 3 months
• If no ejaculation occurs, sperm will dribble into
  terminal ampulla into urethra

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Copulatory organ - penis

• Originates from genital tubercle
• Provides an outlet for both urine and the
  copulatory ejaculate (spermatozoa and seminal
  plasma)
• Histology/anatomy of penis varies from species to
  species and from region to region within the same
  species
• Body of the penis consists of
• the urethra
• erectile tissue (corpora cavernosa penis and
  corpora cavernosum urethra), cavernous bodies act
  as erectile tissues where it can be engorged with
  blood to erect the penis
• touch and pressure receptors (Pacinian
  corpuscles)
• a dense connective tissue capsule (tunica
  albuginea
• tip of penis is called glans penis and in humans
  it is mushroom-shaped

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Penis
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Accessory glands

• A pair of seminal vesicles, prostate glands and
  bulbo-urethral glands (Cowpers glands)
• Originates from urogenital sinus and mesonephric
  ducts
• Produces seminal plasma which is the fluid
  component of semen

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• seminal vesicle empties contents into ampulla
• tubuloalveolar gland
• yellowish secretory product and contains
  fructose, citrate, ascorbic acid, inositol,
  prostaglandins and proteins
• fructose is an important energy source for
  spermatozoa
• 70 of ejaculate (semen) derives from the seminal
  vesicles
• secretory activity stimulated by testosterone
• prostrate gland empties contents into the
  prostatic urethra
• prostrate is a branched tubuloalveolar gland
• secretions include acid phosphatase, amylase, and
  fibrinolysin
• gland wraps around prostatic urethra and empties
  into it
• glycoprotein deposits develop and can become
  calcified, these are called prostatic concretions
  or corpora amylacea and are a characteristic
  feature of the adult prostrate
• secretory activity stimulated by testosterone
• hyperplasia occurs within the gland with
  increasing age, gradually decreasing the
  diameter of the urethra and slowing urine voiding

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• bulbourethral (Cowpers) gland empty into the
  post-prostatic urethra
• tubuloalveolar glands that secrete a lubricating
  mucous that contains galactose, galactosamine,
  galacturonic acid, sialic acid, and methylpentose
• secretions precede other ejaculatory products and
  release involves the oxytocin axis
• secretory activity of epithelia stimulated by
  testosterone

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Seminal plasma

• Three functions
• as a media that provides the suspension/vehicle
  and also activation to spermatozoa
• provides electrolytes, nitrogen, citric acid,
  fructose etc for nutrition
• provides an alkaline pH to semen to combat
  acidity of vagina

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Spermatozoa

• A very simple cell but highly adapted for
  reaching and penetrating the ovum
• Basically have head, midpiece and tail
• Different sizes in different species
• Head shape may be paddle (human, rabbit, bull,
  ram), cylindrical (cockerel) or hooked (rodent
  species)
• Acrosome in the head contains hydrolytic enzymes
  for digesting cells around ovum can also digests
  sperm upon death
• Carries the necessary package for fertilization
  (enzymes and chromosomes) Needs to travel light
  as main function is for fertilization
• Tail contains mitochondria that provides ATP for
  energy for increased motility to reach ovum
  before sperm dies
• Tail have 9 2 doublets arrangement called
  axoneme
• Has no energy reserves, hence has a limited life
  span once released (48 72 hrs)
• Dies by degeneration (hydrolytic enzymes in
  acrosome destroy sperm upon death)

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Spermatozoa

Rat sperm
Rabbit sperm
Human sperm
Chicken sperm
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Sperm motility
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Semen

• Ejaculate - spermatozoa and seminal plasma
• By volume lt10 sperm
• Accessory Glands 60 seminal vesicle,
• 10 bulbourethral, 30 prostate
• Usually ph 7 to 7.4
• Coagulate after ejaculation in human
• Coagulation is important so that sperm
• number that enters vagina is maintained
• Liquefaction of semen occurs usually before 30
  mins
• Liquefaction is due to enzyme-substrate
  interaction
• The liquefaction time denotes semen quality the
  longer the liquefaction time, the lower is the
  quality. WHY? As the life span of sperm is only
  about 72 hours, the sperm will need to break free
  from the gel ASAP to enable it to swim up to meet
  the ovum

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Normal semen values (WHO,1999)

• Volume 2 3 ml
• Liquefaction time ideally 30 mins)
• Colour Milky
• Viscosity Fairly watery
• pH 7 7.2
• Motility 50 60
• Count gt 20 million/ml
• Viability gt 50
• Normal morphology variable 30

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Terms

• Normospermia/normozoospermia (normal semen
  values)
• Azoospermia no sperm found in sample
• Oligospermia less than 20 million/ml sperm
• Asthenozoospermia sperm present but non-motile
• Necrozoospermia high number of dead sperm
• Teratozoospermia high number of abnormal sperm

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Regulation of spermatogenesis

• Prepubertal LH and FSH are low, thus testes
  activity is low
• Between the ages of 13 and 20 the hypothalamic/
  pituitary/ gonadal axis is reactivated (puberty)
• The precise trigger is not known
• could be percentage body adipose tissue
• could be pineal gland/ melatonin involvement

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Regulation of testicular function

• GnRH released every 2- 3 hours
• Results in a pulsatile release of LH and FSH
• Testosterone from Leydig cells inhibits both the
  release of LH and GnRH
• Inhibin from Sertoli cells inhibits the release
  of FSH (but not LH or GnRH).

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Hormonal influence

• GnRH from hypothalamus goes to anterior
  pituitary FSH and LH are released
• LH (Interstitial Cell Stimulating Hormone/ICSH)
  goes to Leydig cells to initiate production of
  testosterone
• FSH and testosterone stimulates Sertoli cell
  (Sustentacular cells) to increase enzyme activity
  (5?-reductase, aromatase) and synthesis Androgen
  Binding Proteins (ABP)
• ADP will bind to testosterone causing level of
  testosterone in lumen of seminiferous tubules to
  rise
• Sustentacular cells also produce inhibin (a
  peptide hormone)
• FSH and LH only acts on testis but testosterone
  influences testis and initiate development of
  sexual organs and male secondary sexual
  characteristics

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Control of testosterone secretion

• When testosterone and inhibin levels in the blood
  are high, two negative feedback mechanisms are
  initiated to regulate the spermatogenic process
• When levels of circulating testosterone are high
  in the blood, this high testosterone will send a
  negative feedback mechanism to hypothalamus to
  inhibit LH release

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Control of sperm production

• When there are gt20 million spermatozoa in the
  testicles, inhibin will send a negative feedback
  mechanism to the hypothalamus to inhibit the
  release of FSH
• This two negative feedback mechanisms are
  terminated when level of testicular spermatozoa
  falls below 20 million and testosterone level
  falls below required level for normal
  spermatogenesis

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Functions of testosterone

• Produced by the Interstitial cells of Leydig
  under influence of LH and GnRH
• Testosterone has a number of functions
• Promotes maturation of sperm cells
• Maintains male 2nd sex organs
• Determines secondary male characteristics (wide
  shoulders, narrow hips, body hair patterns,
  enlargement of thyroid cart of larynx, deepens
  voice)
• Stimulates bone and muscle growth, epiphysial
  closure, protein metabolism