W12 - MALE REPRODUCTIVE PATHOPHYSIOLOGY

Question 1

What is the site of spermatogenesis?

Answer 1

• The formation of sperm occurs in the seminiferous tubules of the testes and takes approximately 64 to 72 days
• Structure
  
  • Interstitium
    
    • Leydig cells - secrete testosterone
  • Seminiferous tubule
    
    • Sertoli cells - support spermatogenesis to form spermatogonia - form sperm
• Process involves both mitotic (duplication) and meiotic (chromosome halving) cell divisions

Question 2

What are the functions of testosterone?

Answer 2

• Responsible for spermatogenesis and characteristics that define the masculine body
  
  • Production increases rapidly during puberty due to decreased responsiveness of the hypothalamic-pituitary axis to negative feedback
  • Development of male primary sexual characteristics
    
    • Penis, scrotum and testes (8-fold increase in size by age 20)
    • Prostate gland
    • Seminal vesicle
    • Male genital ducts (Including epididymis and vas deferens)
• Development of male secondary sexual characteristics
  
  • Body hair
    
    • Over abdomen, face and chest
  • Baldness
    
    • Decreased growth of hair on top of head
  • Voice
    
    • Hypertrophy of laryngeal mucosa and enlargement of larynx
  • Skin
    
    • Increased thickness, increased sebaceous gland secretions and acne
  • Muscles
    
    • Protein formation and muscle development
  • Bone
    
    • Increase bone matrix and Ca2+ retention
  • Metabolism
    
    • Increased basal metabolism
  • Behaviour
    
    • Promotes sex drive (libido) and aggressiveness

Question 3

What are the causes of male infertility?

Answer 3

• Diverse range of deficiencies
  
  • Sperm formation (morphology)
  • Sperm concentration (e.g. oligozoospermia, azoospermia)
  • Sperm motility/transport/blocked ducts
  • Testicular cancer (associated with impaired spermatogenic function)
  • Hypogonadism (primary and secondary); prolactinoma
  • Chromosomal abnormalities (Klinefelter syndrome)
  • Varicocele; cryptorchidism; orchitis (elevated temperatures)
  • Cigarettes, marijuana, alcohol, stress
  • Drugs (ketoconazole, cimetidine, tetracycline)
  • Toxins (pesticides, lead exposure)

Question 4

Explain cryptorchidism

Answer 4

• 3% of newborns
• Testes remain in abdomen (25%) or inguinal canal (70%)
• Incomplete descent in one or both testes (Depends on androgens)
• Testes exposed to high body temperature = Increased risk of infertility
• Causes spermatogenic cell atrophy and leydig cell hyperplasia
• Men with unilateral cryptorchidism have lower than expected sperm counts
• Treatment
  
  • Gonadotrophins (hCG) or surgery

Question 5

Explain varicocele

Answer 5

• Spermatogenesis only occurs at approximately 4-6°C below body temperature
• Pampiniform plexus
  
  • Venous network surrounding testicular artery in spermatic cord
  • Counter-current heat exchange from arterial to venous blood
• Varicocele
  
  • Engorged spermatic chord veins = Reduced returning blood flow
  • Testes exposed to high body temperature = Increases risk of infertility
  • Causes reduced semen quality

Question 6

Explain the effect of elevated temperature on testis

Answer 6

• Testicular atrophy
  
  • Spermatogenic cells atrophy
  • Leydig cell undergo hyperplasia (risk of testicular cancer)
  • Only sertoli cells colonize tubules

Question 7

What is male hypogonadism? Explain the two classifications of hypogonadism

Answer 7

• Testicular deficiency (develops during gestation or from puberty)
  
  • Decreased testosterone production
  • Decreased sperm production
• Hypergonadotropic hypogonadism (primary)
  
  • Most common cause is Klinefelter’s syndrome (1 case per 500-1,000 live births)
  • Testicular dysfunction = increase circulating gonadotrophins
• Hypogonadotropic hypogonadism (secondary)
  
  • More rare (tumour or Kallmann’s syndrome)
  • Pituitary or hypothalamus dysfunction = decreased gonadotrophins
• Leydig cell deficiency from childhood - eunuchoidism

Question 8

What is Klinefelter’s syndrome? Explain its actions in the testes and some common signs and symptoms

Answer 8

• Most common cause of primary hypogonadism (1 case per 500-1,000 male births)
• Possess extra X chromosome
  
  • 47, XXY (90% cases)
  • 48, XXXY
  • 46, XY/47, XXY (Mosaics)
  • 46 ,XX (SRY translocation)
• Testes
  
  • Leydig cells reduced response to LH (approximately 10-50% testosterone output)
  • Hyalinization and fibrosis of seminiferous tubule - infertility
    
    • Sertoli cell - decreased inhibin = increased FSH
• Gynaecomastia (breast development in males)
  
  • Increased oestradiol:testosterone ratio (peripheral conversion and decreased clearance)

Question 9

What is male hypergonadism? Explain

Answer 9

• Androgen secreting tumours (Very rare)
  
  • Adrenal adenomas (Increases DHEA-S)
  • Leydig cell tumours - 1-3 % cases (increases testosterone)
• Causes low circulating gonadotrophins (LH and FSH)
• Occurs during puberty or later in life
• Signs
  
  • Early puberty (Precocious puberty)
  • Acne
  • Excessive muscle mass
  • Mood swings
  • Breast tissue growth
  • Unusual body hair growth

Question 10

Explain the process of defining sub-fertile sperm. What are the 2010 WHO semen lower reference limits?

Answer 10

• Defining sub-fertile sperm
  
  • Primary laboratory analysis
    
    • Semen analysis (Number, volume, motility, morphology)
  • WHO 2010 semen lower reference limits (Normozoospermia)
    
    • Volume - >1.5 mL (1.4 - 7.6 mL)
    • pH - ≥7.2
    • Sperm count - >15 million/mL (Concentration); >39 million (Total)
    • Morphology - >4% normal
    • Motility - >32% (Progressive); >40% (Total)
    • Viability - >58% live
  • Sub-fertile sperm
    
    • Oligozoospermia - <15 million/mL
    • Azoospermia - no sperm
    • Aspermia - no ejaculate

Question 11

What are some assisted reproductive technologies for male infertility treatment

Answer 11

• Assisted reproductive technologies
  
  • Intrauterine artificial insemination (IUAI)
    
    • Introduction of sperm into uterus by catheter
    • For sub-optimal sperm motility or numbers
  • Conventional in vitro fertilization (IVF)
    
    • Natural fertilization of oocyte in vitro then blastocyst transfer to uterus
    • For very poor sperm motility or numbers
  • Intracytoplasmic sperm injection (ICSI)
    
    • Direct sperm injection into oocyte in vitro then blastocyst transfer to uterus
    • Often for immotile or fertilization incompetent sperm