Spermatogenesis

Question 1

Major functional components of the testes?

Answer 1

• Seminiferous Tubules - ~250m total length, has developing germ cells and sertoli cells.
• Interstitial Spaces - have leydig cells (synthesise androgens) and blood & lymph vessels.
• Compartments held by separate by blood-testis barrier which prevents immune response to spermatozoa and separates fluid of different composition.

Question 2

3 stages of spermatogenesis

Answer 2

• Mitotic proliferation
• Meiotic divisions
• Cell modelling (spermiogenesis)

Question 3

Spermiation

Answer 3

At the end of differentiation; cytoplasmic links are broken, spermatozoa released into tubule lumen, and sperm are virtually immobile.

Fluid secreted by Sertoli cells flushes spermatozoa from seminiferous tubules, through the Rete Testis into the Epididymis: Capacity for motility by the time they reach the tail of the epididymis, motility is suppressed by epididymal fluid and instead movement through reproductive tract is aided by peristaltic muscle contractions.

Question 4

Spermiogenesis

Answer 4

Spermatocyte > Spermatid > Spermatozoon

About 200million/day (approx. 2300/second)

Question 5

Spermatogenic Cycle

Answer 5

Stem Cell > Type A Spermatogonia > Intermediate Spermatogonia > Type B Spermatogonia > Resting Primary Spermatocyte > Stages of meiosis (leptotene, zygotone, pachytene, diplotene) > secondary spermatocyte (formed by first meiotic division) > spermatid (formed by second meiotic division) > Spermatozoon.

Question 6

Average length of Spermatogenic Cycle?

Answer 6

~74 days from 1st mitotic division to release of spermatozoa.

Question 7

Spermatogenesis - Rate of each developmental stage?

Answer 7

• Spermatogonium - Primary Spermatocyte - 25 days
• Meiotic Division 1 - Secondary Spermatocyte - 9 days
• Development - Spermatids - 19 days
• Differentiation - Spermatozoa - 21 days

Question 8

Processes of Sperm Maturation

Answer 8

• Development of motility
• Nuclear maturation
• Water loss
• Acrosome changes shape
• Surface charge changes
• Permeability of membrane changes
• Cytoplasmic droplet is shed
• Cellular lipid reserves are depleted
• Sialic acid glycoprotein coat is gained

Question 9

Changes made to the Spermatozoa in the Epididymis

Answer 9

• Concentration - 10-fold (10^8/ml entering > 10^9/ml leaving)
• Sperm modelling - nuclear condensation and acrosome shaping completed. Cytoplasmic droplet is shed.
• Metabolism - increased dependent on extracellular fructose for glycolytic energy, little oxidative metabolism, increase intracellular pH (due to Na+/H+ exchange).
• Motility - increased disulphide bridges between proteins in outer dense fibres of tail. increased concentration of cAMP in the tail. Acquires the capacity for forward movement.
• Membrane - composition changes.

Question 10

Sub-fertility

Answer 10

• Human sperm quality is poor - only 4-14% show normal morphology under the microscope.
• If normal morphology drops below 4% fertilisation rates obtained with IVF are reduced.
• Infertility in men is primarily diagnosed by semen analysis comprising of: determination of sperm concentration/total count, motility, morphology.

Question 11

Oligozoospermia

Answer 11

Reduced sperm count (<15million/ml)

Question 12

Azoospermia

Answer 12

Absence of sperm in the ejaculate

Question 13

Asthenozoospermia

Answer 13

Reduced sperm motility (<40% moving)

Question 14

Teratozoospermia

Answer 14

Reduced percentage of sperm with normal morphology

Question 15

Anti-sperm Antibodies

Answer 15

Abnormal immune response to sperm

Question 16

Roles of Hypothalamus and Pituitary in Spermatogenesis

Answer 16

Hormones released by the hypothalamus, pituitary and testes sre regulated by feedforward and feedback loops. Hypothalamic secretion of Gonadotrophin-releasing hormone (GnRH) stimulates the release of gonadotrophins from the anterior pituitary. Pituitary gonadotrophins, luteinising hormone and follicle-stimulating hormone control testicular functions.

Question 17

Control of Gonadotrophin Secretion

Answer 17

• LH and FSH secretion is controlled by GnRH secreted by the hypothalamus.
• GnRH is released into the portal blood in pulses every hour.
• GnRH must be pulsatile or it is ineffective.
• High GnRH pulse amplitude and frequency preferentially stimulates LH synthesis and secretion whereas low GnRH pulse frequency stimulates FSH synthesis and secretion.

Question 18

Anterior Pituitary Hormones

Answer 18

• Gonadotrophs - secrete LH and FSH (glycoproteins), most cells secrete one or other, but some secrete both.
• Lactotrophs - secrete prolactin (protein)

Question 19

Posterior Pituitary Hormones

Answer 19

• Neurosecretory neurones - secrete arginine vasopressin (AVP) and oxytocin (peptides).

Question 20

Functions of Luteinising Hormone and Follicle Stimulating Hormone in Spermatogenesis

Answer 20

• Luteinising Hormone - stimulates synthesis and secretion of testosterone in Leydig cells. If LH is too low, testosterone is low and spermatogenesis halts.
• Follicle Stimulating Hormone - required for maximum sperm production and acts on Sertoli cells. Increased androgen receptors, increased FSH receptors. FSH increased RNA and protein synthesis, increased fluid secretion, increased inhibin synthesis and secretion, increased ABP secretion, increased cAMP and cell metabolism.

Question 21

Testicular Hormones

Answer 21

• Testosterone - steroid hormone made by the Leydig cells. In some tissues it does not exert direct effects but are converted to dihydrotestosterone or oestrogens
• Oestrogens - steroid hormone made by the aromatisation of Testosterone in Sertoli Cells
• Inhibins - peptide hormone made in Sertoli cells, helps with the feedback loop to control hormone levels
• Oxytocin - peptide hormone made by Leydig cells. Causes contraction of smooth muscle of the genital tract.

Question 22

Role of Testosterone in Spermatogenesis

Answer 22

Essential for spermatogenesis, if not produced spermatogenesis ceases. It is blocked when primary spermatocytes enter the meiotic prophase.

If blood testosterone concentration is low then fewer stem cells will begin to divide but the whole process of spermatogenesis will still take 74 days.

Question 23

Causal Diagnosis of Male Infertility

Answer 23

• It is not very common for men to receive a causal diagnosis of why they are infertile (~28%); most consist of previous gonadotoxic chemo- or radio-therapy for the treatment of malignant disease (~10%), testosterone abuse or other chronic diseases (e.g. diabetes; ~14%), or genetic disorders (e.g. Klinefelter’s syndrome, Karyotype 47, XXY or microdeletions on the Y-Chromosome; 4%).
• In addition, genes involved in the migration of GnRH neurons or upstream regulators have been discovered that may be mutated in patients with congenital hypogonadotropic hypogonadism with or without anosmia.
• Thus ~72% of men in infertile couples, no causal diagnoses can be established and the aetiology of distubed spermatogenesis remains unclear.