lecture 5: spermatogenesis and testis endocrinology

Question 1

Why is there less fur over the scrotum in the mouse?

Answer 1

• temperature control

Question 2

What is the morphology of sperm?

Answer 2

• very highly differentiated
• huge variation between species but all have same basic structure:
– highly condensed DNA in nucleus, can either be at one end or part way along
– some sort of flagella-like structure that gives motility
– mitochondria rich zones in bulges of cytoplasm, generate the energy to make that flagellum flap
• basic structure is the same, but a lot of variation in exactly how things work

human sperm:
• head, midpiece, tail
• functional segregation

Question 3

What is the structure of a sperm?

Answer 3

head:
• acrosomal cap: cytoplasmic vesicle that contains hydrolytic enzymes and other chemicals involved in fertilisation 
– varies between species
– e.g. wrapped right around apex of head in mammalian sperm   
• anterior band
• equatorial segment 
• serrated band
• post-acrosomal region 
• posterior ring 

middle piece
• series of mitochondria
• bottom of the microtubules that extend into the tail

annulus

principle piece 
 • constructed of pairs of microtubules 
• 9 pairs of outer dense fibres 
• central pair 
• fibrous sheath 

end piece

Question 4

What is spermatogenesis? How does it occur?

Answer 4

• formation of sperm
• start off with a stem cell: spermatogonium
• spermatogonia are mitotic cells, so able to keep on producing new cells via cell division throughout the male’s life
• some of these cells will become committed to meiosis
• start becoming spermatocytes
• A0 → A1 → A2 → A3 → A4 → intermediate spermatogonia → B-type spermatogonia
→ primary spermatocytes
→ secondary spermatocytes
→ early spermatids
→ late spermatids
• A0 - A4 are types of spermatogonia undergoing mitotic divisions leading up to producing a primary spermatocyte that undergoes meiosis I
• A0 as stem cells can produce A1 and A0
• spermatocytes and spermatids all connected via cytoplasmic bridges
• allows for synchronisation so the sperm can mature as a cohort
• final stages of sperm maturation involve getting rid of all the excess cytoplasm
• buds off as a residual body
• variation between species but essentially we have a series of mitotic divisions until we meet a stage where we go to meiosis
• for every spermatogonium that decides to go through to meiosis we get a lot of sperm
• at any stage in a tubule you have four waves of sperm forming
• spermatogenic cycle represents the production of the sperm

Question 5

What is the spermatogenic cycle?

Answer 5

• production of sperm
• time for completion spermatogenesis (days) and duration of cycle of the seminiferous epithelium (days)
• man: 64 and 16
• bull: 54 and 13.5
• ram: 49 and 12.25
• boar: 35 and 8.5
• rat: 48 and 12
• the duration of the spermatogenic cycle is constant and characteristic for each species

Question 6

How is it all controlled?

Answer 6

• governed by the pituitary gland
• hypophysectomy (removing pituitary) stops steroidogenesis and spermatogenesis
• SFs of hypophysectomised rat shows almost no lumen, no maturing sperm
• get a little way through meiosis before packing in because they need LH and FSH
• FSH tells sertoli cells to mature the sperm
• testosterone can also act like FSH in high concentration
• LH makes leydig cells produce testosterone in the interstitium

Question 7

What is the relationship between FSH and the Sertoli cell?

Answer 7

• FSH receptor in basal cell membrane 
• acts via cAMP and Ca++ 
• acts with T to support spermatogenesis 
• stimulates 
– mRNA and protein synthesis 
– glucose transport 
– lactate production 
– inhibin 
– ABP
– transferrin
– aromatase 
– mitosis (in immature S.C.)

Question 8

Describe that weird diagram

Answer 8

• blood vessels in interstitial tissue
• leydig cell makes testosterone
• converted to oestradiol in the SC (lil in the LC)
• also 5-alpha DHT
• more potent androgen
• DHT
• LH in the blood acts on LH receptor on LC to accentuate cholesterol to pregnenolone step - rate limiting step
• LH is coming from the pituitary gland

Question 9

What is the hypothalamo-pituitary-gonadal axis ?

Answer 9

• Hypothalamus acts on pituitary
• releases GnRH
• acts on gonadotropes to increase LH and FSH secretion
• sertoli cells produce inhibin which inhibits FSH secreting cells in pituitary
• negative feedback loop bc FSH stimulates SC to produce inhibin
• LH tells leydig cells to produce testosterone which circulates around the blood /body
• –ve feedback effects: can shut down GnRH (less LH)
• hormones tend to be fairly steady
• testosterone injection suppresses LH secretion
– decrease pulse frequency
– decrease pulse amplitude
• in rodents DHT has same effect as T

Question 10

For what is LH essential?

Answer 10

• Leydig cell steroidogenesis
• LH receptors present on Leydig cells
• act primarily via cAMP
• raising cAMP increases LC steroidogenesis
• blocking GnRH results in less LH production however FSH production does not change

Question 11

What evidence do we have for the control of sertoli cell function?

Answer 11

• hypophysectomy: low LH/FSH, spermatogenesis halted, accessory sex glands regress
• immunisation against GnRH and pure FSH: partial spermatogeneis resumed, ASG regressed
• hypophysectomy and high dose testosterone: spermatogenesis resumed at reduced level, ASG redevelop