Male Reproduction

Ronald L. Urry, Ph.D., H.C.L.D.
Professor
Department of Urology and Andrology
U of U College of Medicine

To understand hypothalamic-pituitary-testicular hormonal axis and the role of hormones in spermatogenesis.
To understand the process of sperm production.
To know the role of and the markers for epididymis, vas deferens, seminal vesicles, and the prostate.
To understand male fertility problems including: (a) diagnosis of male infertility, (b) traditional treatment of male infertility, and (c) advanced reproductive techniques.

Aspermia: The failure to produce an ejaculate.

Asthenospermia (azthenozoospermia): The production of an ejaculate in which less than 50% of spermatozoa are motile.

Azoospermia: The production of an ejaculate devoid of spermatozoa.

Oligospermia (oligozoospermia): The production of an ejaculate containing less than 20 x 100 spermatozoa per milliliter of semen.

Teratospermia (teratozoospermia): The production of an ejaculate in which more than 50% of spermatozoa are of abnormal shape.

Outline

Hormones and Male Reproduction

Hypothalamus
Pituitary
Testicle
Epididymis
Accessory organs
Male infertility

Outline

Hormones and Male Reproduction

Hypothalamus
1. GnRH (LHRH) contributes to the release of both LH and FSH from the pituitary.
Pituitary
1. FSH release is controlled by the feedback of inhibin from the testicle.
2. LH release is controlled by the feedback of steroids from the testicle.
3. LH and FSH also control their own release by feeding back to hypothalamus.
4. The target organs for FSH and LH are:
  1. LH acts on the Leydig cells to increase steroidogenesis.
  2. FSH participates in protein synthesis and the initiation of spermatogenesis at the level of the seminiferous tubules.
Testicle
1. LH binds to Leydig cells and increases cAMP which increases protein secretion and the side-chain cleavage of cholesterol, as well as other likely steps, to increase steroidogenesis and the production of testosterone and other androgens. Regulated by steroid feedback. The Leydig cells produce the testicular steroids, lie between the seminiferous tubules, and assist in the transportation of steroids in the blood, lymph and seminiferous tubules.
2. FSH binds to the Sertoli cells of the seminiferous tubules, increases cAMP and protein synthesis, androgen binding in the tubules, etc. Regulated by inhibin produced by the Sertoli cells. Sertoli cells secrete proteins that are important to spermatogenesis and have been called the director cells of spermatogenesis. They comprise the blood-testis barrier.
3. Prolactin may increase Leydig cell response to LH and/or prostate sensitivity to androgens.
4. Steroids and other hormones may aid in the movement of sperm from the testicle by causing smooth muscle contractions.
5. Normal hormone values:
  
  FSH = 1-10 mIU/ml
  LH = 1-10 mIU/ml
  Testosterone = 3-10 ng/ml
  
  Estradiol and dihydrotestosterone = extremely low in normal males.
6. Spermatogenesis occurs with the following steps:
  1. Yolk sac endoderm gives rise to primordial germ cells which give rise to more type A cells, some of which degenerate.
  2. Type A stem cells form additional type A cells or differentiate into type B spermatogonia cells during early puberty.
  3. Type B cells differentiate during late puberty and in the adult to form primary spermatocytes, secondary spermatocytes and spermatids. These events occur initially through mitosis and then reduce the chromosomes to one-half through miosis.
  4. Spermiogenesis transforms early spermatids into late spermatids and form what we recognize as morphological normal sperm.
  5. The above process takes 72 to 74 days in the human.
  6. Sperm are released into the lumen through spermiogenesis which involves a gradual release of sperm from the Sertoli cells into the tubule lumen.
  7. Disorders of spermatogenesis can occur and can include:
    1. Azoospermia including Sertoli cell only syndrome
    2. Maturation arrest at one of a number of possible stages
    3. Hypospermatogenesis
  8. Sperm transport from the testicle occurs through:
    1. Seminiferous tubule contractions of the myoid cells (hormone dependent)
    2. Fluid build up and pressure
    3. Testicular capsule contractions
Epididymis
1. Responsible for sperm maturation and motility.
2. Usually two-thirds of the epididymis is needed for sperm transport in the human for normal sperm fertilization capacity.
3. Potential markers of epididymal function include carnitine and glycerol phosphocholine.
4. Sperm take approximately two weeks to get through the epididymis.
5. Sperm are stored near the tail portion and in the vas deferens until they are ejaculated.
Accessory organs
1. Seminal vesicles
  1. Contribute prostaglandins and fructose.
  2. Contribute two-thirds of volume of ejaculate.
  3. Qualitative fructose is useful for verifying presence and the presence of the vas deferens.
2. Prostate
  1. Contributes acid phosphatase, Zn and citric acid.
  2. Chronic inflammation may contribute to infertility.
  3. Many markers including PSA
3. Vas deferens
  1. Sperm storage and transport organ
  2. Adrenergic innervation
Male infertility
1. Contributes to about 50% of infertility.
2. Many potential causes including:
  
      Varicocele
      Idiopathic
      Testicular failure
      Obstruction
      Cryptorchid
      Volume
      Agglutination
      Sexual dysfunction
      Viscosity
      Ejaculatory failure
      Endocrine
      High density
      Necrospermia
      Combination of sperm defects
3. Varicocele contributes to about 40%; idiopathic causes are about 25%.
4. Diagnosis
  1. Physical exam
    1. Testicular size and consistency
    2. Varicocele - usually on the left side; on both sides or right about 10% of the time.
  2. Semen quality
    1. Two or more complete semen analyses
    2. Should evaluate volume, agglutination, viscosity, quantitative motility and morphology, count, viability and membrane quality.
  3. Blood hormones
    1. FSH
    2. LH
    3. Testosterone
    4. Prolactin
  4. History
5. Treatment of male infertility
  1. Specific medical
    1. Gonadotropins - HCG, Pergonal, Metrodin
    2. Other - thyroid, adrenal, etc.
  2. Non-specific medical therapy
    1. Gonadotropins - 2500 IU HCG 2X weekly - 10 to 12 weeks
    2. Testosterone rebound therapy
    3. Clomiphene citrate - 25 mg daily for 3 to 4 months
  3. Varicocele
    1. Semen pattern of low motility, high tapered and immature sperm
    2. Post-surgery correction yields pregnancy rates of 30% to 60% and semen improvement rates of 60% to 80%.
  4. Laboratory improvement of sperm with insemination
    1. Can make semen quality better with lab manipulation techniques and then utilize with intrauterine insemination.
  5. Laboratory improvement with advanced reproductive techniques
    1. GIFT techniques
    2. IVF techniques
      1. Regular IVF
      2. ICSI techniques for poor sperm quality
      3. Sperm aspiration or testicular biopsy with ICSI

Take Home Points

The history, physical exam, and laboratory investigations will detect an etiology for male factor infertility in approximately 50% of cases. Serum FSH levels provide an important diagnostic parameter in determining the pathological basis of azoospermia. Karyotypic analysis is most helpful in males with azoospermia and small testes. Obstruction of the ejaculatory ducts can be diagnosed by ultrasound. The absence of the vas deferens can be detected by the absence of fructose in the semen sample.

The most common congenital abnormality resulting in testicular dysfunction is cryptorchidism. *The longer the testis remain outside the scrotum, the greater the degree of spermatic disruption. The most common chromosomal abnormality resulting in deficient testicular function is Klinefelter's syndrome. The frequency of this abnormality is 1 in 500 live births. The 47,XX7 karyotype results in the destruction of all germ cells with seminiferous tubules causing small, firm testes and azoospermia. Gynecomastia and various degrees of androgen deficiency are usually noted. The most common vascular abnormality associated with infertility is a varicocele. The higher frequency of varicocele in infertile men (21% to 41%) compared to men in the general population (4$ to 23%) has been interpreted as supporting a causal relationship between varicocele and infertility. Theories to account for adverse testicular function with a varicocele include: vascular stasis, back pressure, interference with oxygenation, reflux of renal or adrenal products into the panipiniform plexus and interference with heat exchange function of the panipiniform plexus.

Human Reproduction : Clinical, Pathologic and Pharmacologic Correlations.
Copyright C. Matthew Peterson, M.D., 1997