During the service, the pastor asked if anyone in the congregation would like to
express thanks for prayers which had been answered.
A lady stood up and came forward.
She said, "I have a reason to thank the Lord. Two months ago, my husband, Jim,
had a terrible bicycle wreck and his scrotum was completely crushed. The pain
was excruciating and the doctors didn't know if they could help him."
You could hear an audible gasp from the men in the congregation as they
imagined the pain that poor Jim experienced.
She continued, "Jim was unable to hold me or the children and every move
caused him terrible pain. We prayed as the doctors performed a delicate
operation. They were able to piece together the crushed remnants of Jim's
scrotum and wrap wire around it to hold it in place."
Again, the men in the Congregation squirmed uncomfortably as they imagined
the horrible surgery performed on Jim.
She continued, "Now, Jim is out of the hospital and the doctor's say, with time, his
scrotum should recover completely."
All the men sighed with relief.
The pastor rose and tentatively asked if any one else had anything to say.
A man rose and walked slowly to the podium.
He said, "Hi, I'm Jim and I would like to tell my wife, the word is 'sternum.' "
The real story of the snake in the Garden of Eden …
Dictionary definitions
directile disfunction:
the inability of males, when “geographically
embarrassed” (lost), to stop and ask for
directions.
BIOL30001
Reproductive Physiology
Spermatogenesis
and testicular
endocrinology
Geoff Shaw
Reading:
EssRepro7 Chapters 1, 6, 7
Sharpe (1994) Regulation of spermatogenesis. In Knobill & Neill. The
Physiology of Reproduction vol 2
Setchell B (1982) Spermatogenesis and spermatozoa. In Reproduction
in Mammals V1, Eds Austin CR & Short RV
Knobill & Neill. (eds) (1994) The Physiology of Reproduction vol 2,
chaps 20-22
Endotext.com and most good endocrinology or embryology books
In summary
testis
(sperm production)
epididymis
(sperm transport, maturation and
ejaculation)
efferent ducts
(transport of sperm)
vas deferens
bladder
Cowper’s gland
(secretes a cleansing/
lubricating solution)
(sperm transport and ejaculation)
seminal vesicles
(supply the seminal fluid)
urethra
prostate gland
(passage for semen and urine)
(secretes an alkaline neutralising
solution)
penis
(for copulation)
Sperm morphology
fish
amphibian
birds
mammal
Sperm stained with
fluorescent dyes
that highlight head,
midpiece and tail
structure of a sperm
Please refer to the corresponding figure in
your textbook
J&E fig 4.6
Johnson & Everitt 2000 fig 4.6 (see 6.7)
sperm midpiece and tail
Johnson & Everitt 2000 fig 4.6
entiation
cytodiffer-
meiosis
mitosis
spermatogenesis
sperm development (human)
residual body
DeKretser & Kerr
(1994) Fig 61
LUMEN
spermatid
secondary spermatocyte
primary spermatocyte
Sertoli cells
peritubular
myoid cells
dark A
spermatogonium
pale A
type B
spermatogonium spermatogonia
blood-testis
barrier
spermatogenic epith cycle
different tubule sections have diferent
appearance – a different cohort of spermatogenic
stages- due to spermatogenic wave
RAT
see Johnson & Everitt Figs 4.8 and 4.9
Spermatogenic cycle
species
time for completion
duration of cycle of the
spermatogenesis (days) seminif. epithel. (days)
man
64
16…..
bull
54
13.5..
ram
49
12.25
boar
35
8.5
rat
48
12….
The duration of the spermatogenic cycle is constant and characteristic
for each species
J&E table 4.1
spermatogenic wave on rat
seminiferous tubule
As you go along the seminiferous tubule you
find the sequence of spermatogenic stages
in human tubule you get patches of
spermatogenic initiation
see
Johnson & Everitt 2000 fig 4.10 (6.11)
hypophysectomy stops steroidogenesis
and spermatogenesis
testis of normal rat
testis of hypophysectomised rat
FSH and Sertoli cell
• FSH receptor in basal cell
membrane
• acts via cAMP and Ca++
• acts with T to support
spermatogenesis
• stimulates
–
–
–
–
–
–
–
–
FSH
mRNA and protein synthesis
glucose transport
lactate production
inhibin
ABP
transferrin
aromatase
mitosis (in immature S.C.)
Blood
testicular
steroidogenesis
Sertoli cell
acetate
cholesterol
testosterone
P450scc
pregnenolone
DHEA
androstenediol
3-HSD, 4-5-isomerase
progesterone
androstenedione
testosterone
Leydig cell
Blood
HO
3-HSD
O
ABP
5-dihydro- ABPT
testosterone
oestradiol
androstenedione
oestrone
Tubule
Lumen
LH and control of testicular steroidogenesis
LDL-cholesterol
Blood
Sertoli cell
LH
acetate
LDL-Tr
+
cholesterol
cholesterol
stores
LHR
cAMP
+
testosterone
ABP
ABPT
P450scc
5-dihydrotestosterone
pregnenolone
testosterone
Leydig cell
Blood
Tubule
Lumen
hypothalamo-pituitary-gonadal axis
GnRH
GnRH
-
inhibin
testosterone
LH
FSH
• inhibin from Sertoli cells
specifically inhibits FSH
secretion by pituitary
gonadotropes
LH
FSH
• testosterone injection
suppresses LH secretion
• pulse frequency
• pulse amplitude
• in rodents DHT has
same effect as T
LH is essential for Leydig cell steroidogenesis
hypophysectomy
GnRH
GnRH
GnRH
testosterone
LH
Anti-GnRH
antiserum
FSH
testosterone
LH
Anti-LH
antiserum
testosterone
FSH
reversed by exogenous LH or hCG
• LH receptors present on Leydig cells
• LH acts primarily via cAMP
• raising cAMP increases LC steroidogenesis
LH
FSH
Control of Sertoli cell function
hypophysectomy
GnRH
testosterone
immunization against GnRH
and pure FSH
GnRH
LH
FSH
testosterone
hypophysectomy and
high dose testosterone
GnRH
LH
testosterone
LH
FSH
FSH
spermatogenesis halted
accessory sex glands regress
partial spermatogenesis
resumed (block at A3-A4)
spermatogenesis resumed
at reduced level
ASG regressed
ASG re-develop
Summary
• Spermatogenesis
– control by Sertoli cells
– Spermatogonia  mitotic + meiotic differentiation
•
•
•
•
Spermatogonia
Spermatocytes
Spermatids
Sperm
– Spermatogenic cycle
– Spermatogenic wave
• Hormone production
–
–
–
–
androgen – Leydig cells  Testosterone
Sertoli cells  E2, DHT
inhibin – Sertoli cells
feedback control via hypothalamo-pituitary axis (HPA)
Other control of testis?
• secretagogues in circulation or made in testis (eg
CRF, opiates, catecholamines etc) can alter Leydig
cell activity independently of gonadotrophins
• splanchnic nerves regulates LH receptors and
testicular blood flow
• injection of IL1, CRH or -adrenergic agonists
reduces testicular response to exogenous hCG
see Campos et al (1993) Neuroendocrinology 57:189
Dufau ML (1988) Annu Rev Physiol 50:483
role of oestrogen in spermatogenesis
ER-knockout disrupts spermatogenesis and causes infertility in males
probably by disrupting fluid resorption in efferent ducts
from: Eddy et al (1996) Endocrinology 137:4796-4805
neuroendocrine control of the testis
GnRH
GnRH
testosterone
inhibin
testosterone
inhibin
LH FSH
castrate – about 10ng/ml,
pulses every hour to 14
ng/ml
intact about 1 ng/mlpulses every 2 h to 4
ng/ml
LH
FSH
HPG axis in ram
castrated rams (wethers) + T, DHT, E2 or
control
GnRH
T,DHT,E2 or oil
LH FSH
GnRH
infusion
T,DHT,E2 or oil
all treatments:  LH,  FSH
 pulse frequency
hypothalamo-pituitary (HPD) disconnected
wethers with GnRH pulses infused
every 2 h
LH FSH
all treatments: no effect on LH or FSH
wethers - portal blood samples for GnRH
± testosterone
GnRH
T or oil
LH FSH
effect of T:
 GnRH conc.,
 GnRH pulse frequency
 GnRH pulse amplitude
based on Tilbrook AJ, et al. (1991) Endocrinology 129:3080-92
direct neural control of testicular
testosterone
production?
• injecting transganglionic retrograde nerve tracer into testis marks spinal cord,
brain stem and hypothalamus
SPINAL CORD TRANSSECTION
CONTROL
hCG
hCG/icv CRF
hCG/icv CRF
testosterone
testosterone
hCG
vehicle
0
60
time (mins)
vehicle
0
60
time (mins)
• effect not due to changes in endogenous LH secretion or testicular blood flow
Lee, Miselis & Rivier (2002) Endocrinology 143: 4447-54
Selvage et al. (2004) Endocrinology 145: 1750-9
round spermatids to
elongated spermatids
spermatocytes to
round spermatids
spermatogonia to
spermatocytes
rats intact or
hypophysectomised
and given control
implant or testosterone
implant 3cm or 10 cm
long for 13 weeks
intact
hypophysectomised
from Sun et al (1990)
Endocrinology 127:1215