16-03-23 - Spermatogenesis Flashcards
Learning outcomes
- Describe the major structural and functional components of the testes.
- Describe the stages and chronology of spermatogenesis
- Compare the different sperm abnormalities and recognise how these contribute to male infertility
- Summarise the roles of testicular, pituitary and hypothalamic hormones in regulating testicular function.
Structural Anatomy of the Testis diagram
Cross-section of seminiferous tubules histology
Cross-section of seminiferous tubules diagram
What are the 2 major compartments of the testes?
What is in each compartment?
What are the compartments separated by?
What forms this barrier?
What is the function of this barrier?
- 2 major compartments of the testes:
1) Seminiferous tubules
* ~250 m total length
* Developing germ cells
* Sertoli cells
2) Interstitial spaces
* Leydig cells (synthesize androgens)
* Blood and lymph vessels
- These compartments are held separate by “Blood-testis barrier” which is formed from interactions between adjacent Sertoli cells
- This prevents immune reaction to spermatozoa and separates fluids of different composition
What is spermatogenesis? What are the 3 stages of spermatogenesis?
How many spermatozoa are produced for every primary spermatocyte?
- Spermatogenesis is the production of mature spermatozoa from undifferentiated germ cells (primordial germ cell)
- 3 stages of spermatogenesis:
1) Mitotic proliferation
2) Meiotic divisions
3) Cell modelling (spermiogenesis) - 4 spermatozoa are produced for every primary spermatocyte
How long is the spermatogenic cycle?
How often does spermatogenesis occur?
How long does each developmental transition in spermatogenesis take?
Can the process of spermatogenesis be sped up?
- The Spermatogenic cycle is ~74 days (from 1st mitotic division to release of spermatozoa)
- Spermatogenesis occurs in waves, initiated every 16 days
- Rate of each developmental stages is not uniform:
1) Spermatogonium to 1˚ spermatocytes = 25 days
2) Meiotic division 1 to 2˚ spermatocytes = 9 days
3) Development to spermatids = 19 days
4) Differentiation to spermatozoa = 21 days
- Spermatogenesis cant be sped up, only stopped or slowed down
Spermatogenic cycle diagram
What is spermiogenesis? When does spermiogenesis begin?
How many spermatocytes go through this process a day?
- Spermiogenesis is the process by which haploid round spermatids (spermatocytes) complete a series of events to become streamlined spermatozoa capable of motility.
- Spermiogenesis begins after spermatocytes complete 2 quick successive meiotic reductive divisions to produce haploid round spermatids (spermatocytes)
- About 200 million spermatocytes go through spermiogenesis a day
What 2 processes occur at the end of differentiation?
How mobile are sperm at this point?
What process needs to occur at this point?
What is spermiation?
When will these mature spermatids be able to have capacity for motility?
What is motility suppressed by?
How is movement through the reproductive track aided?
When will sperm reach full motility?
- 2 processes that occur at the end of differentiation:
1) Cytoplasmic links are broken
2) Spermatozoa released into tubule lumen - Sperm are virtually immobile at this point
- Spermiation needs to occur at this point, which is the final stage of spermiogenesis
- Spermiation is the process by which spermatozoa are released in fluid from Sertoli cells into the seminiferous tubule lumen prior to their passage into the rete testis then the epididymis
- The spermatozoa will have capacity for motility by the time they reach the tail of the epididymis
- Motility is suppressed by epididymal fluid
- Instead, movement through reproductive tract is aided by peristaltic muscle contractions
- Sperm will reach full motility in the female reproductive tract
What 9 processes are seen in sperm maturation?
When are these processes needed?
- 9 processes seen in sperm maturation:
1) Development of motility
2) Nuclear maturation
3) Water loss
4) Acrosome changes shape
5) Surface charge changes
6) Permeability of membrane changes
7) Cytoplasmic droplet is shed
8) Cellular lipid reserves are depleted
9) Sialic acid glycoprotein coat is gained - These processes are needed before fertilization can occur
Changes to spermatozoa in the epididymis (in picture):
* Concentration (1)
* Sperm modelling (2)
* Metabolism (2)
* Motility (3)
* Membrane (1)
What is sperm quality like?
What % show normal morphology?
How can morphology rates affect IVF?
How is infertility in men primarily diagnosed?
- Human sperm quality is poor
- Only 4-14% of sperm show normal morphology under a microscope If normal morphology drops below 4% fertilization rates obtained with IVF are reduced
- Infertility in men is primarily diagnosed by semen analysis comprising of:
1) Determination of sperm concentration/total count
2) Motility
3) Morphology
What are the following WHO reference ranges for:
* Semen volume
1) pH
2) Sperm concentration
3) Total sperm count
4) Total sperm motility
5) Sperm morphology
- WHO reference ranges:
1) Semen volume >1.5 ml
2) pH >7.2
3) Sperm concentration >15 million sperm/ml
4) Total sperm count >39 million sperm/ejaculate
5) Total sperm motility >40% motile sperm
6) Sperm morphology
What are 5 different type of sperm abnormalities?
How common is a combination of these abnormalities?
- 5 different type of sperm abnormalities:
1) Oligozoospermia
* Reduced sperm count (< 15 million/ml)
2) Azoospermia
* Absence of sperm in the ejaculate
3) Asthenozoospermia
* Reduced sperm motility (< 40% moving)
4) Teratozoospermia
* Reduced percentage of sperm with normal morphology
5) Anti-sperm antibodies
* Abnormal immune response to sperm
- Combinations of these abnormalities are common
How are hormones released by the hypothalamus, pituitary and testes regulated?
What stimulates the release of gonadotropins from anterior pituitary?
What are the 2 controls of testicular functions?
What are they examples of?
- Hormones released by the hypothalamus, pituitary and testes are regulated by feedforward and feedback loops
- Hypothalamic secretion of Kisspeptin induces the secretion of Gonadotrophin-releasing hormone (GnRH) which in turn stimulates the release of gonadotropins from anterior pituitary
- 2 controls of testicular functions:
1) Luteinizing hormone (LH)
2) Follicle stimulating hormone (FSH) - LH and FSH are pituitary gonadotrophins
What is LH and FSH secretion controlled by?
How often is GnRH released?
Why is this necessary?
What does high and low GnRH pulse amplitude and frequency preferentially stimulate?
- LH and FSH secretion are 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
What cells have LH receptors?
What does this stimulate?
What happens to testosterone levels if LH secretion is too low?
What else is also needed for spermatogenesis?
What is needed for maximum sperm production?
What does FSH act on?
Describe the flowchart for hormones regulating spermatogenesis (in picture)
- Leydig cells in the testes have receptors for LH – stimulates synthesis and secretion of testosterone
- If LH secretion is too low, testosterone is low – spermatogenesis halts
- However, LH and testosterone cannot maintain spermatogenesis at its normal level without FSH
- FSH is required for maximum sperm production – acts on Sertoli cells
- Flowchart for hormones regulating spermatogenesis (in picture)
Describe the 6 processes that occur when FSH binds to Sertoli cells.
- 6 processes that occur when FSH binds to Sertoli cells:
1) Increase androgen receptors
* Increased FSH receptors, which increases FSH sensitivity
2) Increased RNA and protein synthesis
3) Increased fluid secretion
* Flushes developing sperm in fluid from Sertoli cells into the seminiferous tubule lumen
4) Increases inhibin synthesis and secretion
* Involved in negative feedback
5) Increase androgen binding protein (ABP) secretion
* Keeps testosterone in high concentrations
6) Increase Camp and cell metabolism
What is testosterone essential for? What happens if testosterone production is prevented?
When is spermatogenesis blocked?
What happens if blood testosterone concentrations are low?
- Testosterone is essential for spermatogenesis
- If production of testosterone is prevented, spermatogenesis ceases
- Spermatogenesis will be blocked when primary spermatocytes enter meiotic prophase
- If blood [testosterone] is low then fewer stem cells will begin cell division but the whole process will still take 74 days.
HPG feedback loops – Summary
