Professional Documents
Culture Documents
“Dr Gillian Lockwood, whose team made the breakthrough, says: "The
technology ... will work just as well for the Bridget Jones generation who want
to freeze their eggs to keep their reproductive options open.“. On ITV1's
Tonight with Trevor McDonald on Friday, she explains: "I think that egg
freezing may come to be seen as the ultimate kind of family planning."
The reproductive
lifespan
Ovarian
cycles
Pregnancy Lactation
Reproductive
potential
Male
Female
Puberty Menopause Age
Menstrual cycle lengths
Reproductive tract
MENSTRUATION
Other targets
What are oestrogens? Ovaries
OH
Testes
CH3 Placenta
Oestradiol-17
HO
Bone
Brain
Answer: Steroids with characteristic effects, esp. on female
reproductive tract. Some are more potent than others.
` Cardovascular
Breast
system
Reproductive tract
“GnRH pulse
Hypothalamus Pulsatile activity of
generator” GnRH neurones
GnRH Pulses of GnRH
Pituitary
LH Pulses of LH
FSH Plasma LH
+
Ovaries
24 hours
Natural suppression Modulation during
Before puberty menstrual cycle
Lactation Diet
Diet induced Stress?
Anorexia
Malnutrition
Exercise
Hypothalamic neurones
“GnRH pulse generator”
Pituitary
Changing patterns of
LH and FSH
Timing events in the menstrual cycle.
1. Onset of menstruation
Day 1 Day 1
0 4 8 12 16 20 24 28
Menstruation
Timing events in the menstrual cycle.
2. LH surge
LH
Days before Days after
Day 1 Day 1
Follicular phase Luteal phase
0 4 8 12 16 20 24 28
Menstruation
OVULATION
Animated ovarian events
LH
1. Follicular
Day 1 growth
0 4 8 12 16 20 24 28
Menstruation Oestradiol
OVULATION
Animated ovarian events
0 4 8 12 16 20 24 28
Menstruation Oestradiol
OVULATION
Animated ovarian events
0 4 8 12 16 20 24 28
0 4 8 12 16 20 24 28
Cumulus
cells
Oocyte
Zona pellucida
(non-cellular glycoprotein coat)
Cumulus
Oocyte cells
Cytoplasmic
bridges from
cumulus cells
to oocyte for
transport
Zona pellucida
(non-cellular glycoprotein coat)
Where do follicles come from?
Male Female
Spermatogonia Primordial germ cells
(oogonia)
Continuous
replacement Mitoses stop
in adult in fetal life
Continuous loss
No. of 99.9% by
germ cells “Atresia”
(millions)
Ovulation
(post-puberty)
Puberty
BIRTH ~ 300,000
3 6 9 1 10 20 40
months years
Conception Age from conception
Growth of follicles:
Antral Graafian
follicle follicle
Primordial
follicle
Oocyte Ovulation
Antrum
Granulosa (fluid filled
cells space)
Thecal
cells
Lets look at follicular growth first… How many follicles
There are a number of questions to ask… reach this point?
Normally 1
Ovulation
Menstruation
Many! 30-50
Ovulation
Menstruation
Many! 30-50 Why is only 1
selected and
becomes
How many follicles
“dominant”?
are growing at the
start of the cycle?
When do
follicles
start
growing? Ovulation
LH
(“gonadotrophins”)
FSH
Steroid
feedback
+
Ovaries
Oestradiol (E2)
+
Reproductive tract
Other targets
What controls
follicular growth? OVULATORY
FOLLICLE
??????
Gonadotrophin
FSH
independent
+ LH
Ovulation
Menstruation
OVULATORY
FOLLICLE
FSH
+ LH
Ovulation
OESTRADIOL
As each follicle grows, it produces
Menstruation increasing amounts of oestradiol.
How is oestradiol Granulosa cells
production controlled ? Theca
LH
Androgens are
converted
Androgens (aromatized) to
oestradiol by the
granulosa cells
(Note: the production of
androgens is a normal
part of ovarian FSH
physiology)
Inhibin OESTRADIOL
(protein) (steroid)
Hypothalamus
_ GnRH
(gonadotrophin
releasing
Pituitary hormone)
FSH
LH
Increasing
amounts of +
oestradiol. Ovaries
Oestradiol (E2)
+
Reproductive tract
Other targets
Hypothalamus
Increasing
negative
feedback
_ GnRH
(gonadotrophin
releasing
Pituitary hormone)
INHIBIN
(suppresses FSH) Decreased
FSH
Increasing
amounts of +
oestradiol. Ovaries
Oestradiol (E2)
+
Reproductive tract
Other targets
As the follicles grow, FSH
levels fall due to the
negative feedback,
FSH
Oestradiol
0 4 8 12 16 20 24 28
Why is only 1
selected and
becomes
Many follicles at
“dominant”?
the start of the
cycle
Ovulation
Menstruation
Hypothalamus
GnRH
Pituitary
FSH
+
Ovaries
GnRH
Pituitary
FSH
+
Ovaries
_
Increasing
negative
feedback GnRH
Pituitary
INHIBIN Decreased
Oestradiol FSH
FSH
+
Ovaries
Large follicles: less
Small follicles:
very dependent dependent on FSH
on FSHOestradiol (E2)
Growth factors
Insufficient Oestradiol Dominant
FSH follicle
+ +
FSH
secretion
suppressed
Insufficient FSH to
keep smaller follicles
going – they become
atretic.
0 4 8 12 16 20 24 28
Polycystic ovaries
The classical picture of PCO: a string of
follicles, 2-8 mm in diameter
LH
Androgens are
converted
Androgens (aromatized) to
oestradiol by the
granulosa cells
(Note: the production of
androgens is a normal
part of ovarian FSH
physiology)
OESTRADIOL
(steroid)
4. The disturbed steroid
feedback may re-inforce the 1. Raised LH, lowered FSH
abnormal LH/FSH secretion
3. The high LH
induces high
androgen secretion 2. ….. leads to
from the theca disturbed follicle
growth
HIRSUTISM ANOVULATION
Disturbed cycles
4. The disturbed steroid
feedback may re-inforce the 1. Raised LH, lowered FSH
abnormal LH/FSH secretion
3. The high LH
induces high
androgen secretion 2. ….. leads to
from the theca disturbed follicle
growth
HIRSUTISM ANOVULATION
Disturbed cycles
4. The disturbed steroid
feedback re-inforces the
abnormal LH/FSH
secretion 1. Raised LH, lowered FSH
3. The high LH
induces high
androgen secretion
from the theca 2. ….. leads to disturbe
follicle growth
HIRSUTISM ANOVULATION
Disturbed cycles
What causes
ovulation?
0 4 8 12 16 20 24 28
What causes
ovulation?
LH
0 4 8 12 16 20 24 28
What effects
does it have?
What causes
the LH surge?
0 4 8 12 16 20 24 28
NOT
HUMANS!
What causes
the LH surge?
Reflex
ovulation
0 4 8 12 16 20 24 28
0 4 8 12 16 20 24 28
Hypothalamus
For most of the cycle,
negative feedback
operates…
_
_ GnRH
Pituitary
LH Inhibited by
FSH oestradiol
Oestradiol
Ovary
BUT, with high
levels of E2
maintained for
Hypothalamus
long enough……
+
+ Pituitary
GnRH
LHLH
FSH
surge
Oestradiol
Ovary
BUT, with high
levels of E2
maintained for
Hypothalamus
long enough……
+ Increased GnRH
+ Pituitary
GnRH
Increased
sensitivity
to GnRH
LHLH
FSH
surge
Oestradiol
Ovary
How does the LH surge
affect the follicle?
About 36 h between LH
surge and oocyte release…..
Oocyte:
• Completion of the 1st meiotic
division (unequal division;
extrusion of 1st polar body)
• Ruptured follicle
becomes solid corpus
luteum
• Thecal cells and blood
vessels invade
• Granulosa cells
hypertrophy and
terminally differentiate
(“luteinisation”).
Oestradiol
Progesterone
Why does the
CL degenerate
at the end of the
cycle?
0 4 8 12 16 20 24 28
OVULATION
What maintains
Hypothalamus
the CL?
8 hr
between GnRH
LH pulses
Pituitary
LH
+
CL
(low levels)
CL very
Progesterone sensitive to LH
+ E2
What maintains
Hypothalamus
the CL?
Steroid negative
- GnRH
feedback keeps
LH and FSH - Pituitary
levels relatively
LH
low
Progesterone
+ E2
+
CL
(low levels in
luteal phase)
CL very
Reproductive tract etc sensitive
Hypothalamus
Towards the end of
the cycle, the
sensitivity to LH
GnRH
reduces.
Pituitary
The low levels of LH
are insufficient to keep LH
the CL going
Progesterone
+ E2 CL degenerates
Hypothalamus
GnRH
As CL degenerates… Pituitary
Progesterone
+ E2
Hypothalamus
GnRH
As CL degenerates… Pituitary
0 4 8 12 16 20 24 28
OVULATION
Oestradiol
Progesterone
0 4 8 12 16 20 24 28
OVULATION
Oestradiol
Progesterone
0 4 8 12 16 20 24 28
OVULATION
Oestradiol
Progesterone
0 4 8 12 16 20 24 28
OVULATION
Other changes in the cycle
0 4 8 12 16 20 24 28
Menstruation
OVULATION
Terminal differentiation of
stromal cells – “decidualisation”
0 4 8 12 16 20 24 28
Optimal time for
Menstruation implantation
What causes the onset of menstruation?
Steroid
levels
fall This is followed
by the onset of
menstruation
1. At end of the luteal phase, steroid production declines.
2. Loss of oedema and gradual shrinking of endometrial tissue. The
spiral arteries become more highly coiled
3. Gradual reduction in blood flow to superficial layers – leading to
ischaemic hypoxia and damage to the epithelial and stroma cells.
4. 4‑24 hours prior to menstrual bleeding, an intense constriction of
spiral arteries occurs.
5. Individual arteries re-open at different times, tearing and
rupturing the ischaemic tissues.
6. Bleeding into the cavity occurs via:
1. red cells diapedese between surface epithelial cells;
2. tears develop in the surface epithelium
3. pieces of weakened superficial endometrium crumble away
7. About 50% of degenerating tissues is resorbed and 50% is lost as
'menstrual bleeding'.
Onset of menstruation is rapid.
0 4 8 12 16 20 24 28
Abundant mucus
- like “raw egg
Production
white”
of low Cervical
viscosity mucus
mucus
increases Thick, rubbery, high
Variable viscosity -
number of impenetrable to
“dry” days sperm.
0 4 8 12 16 20 24 28
Menstruation
OVULATION
With increasing oestradiol:
3. Increased elasticity –
("spinnbarkeit test")
0 4 8 12 16 20 24 28
Menstruation
OVULATION
Anovulatory cycle?
Fertility
LH
Ovulation
Oestradiol
Progesterone
0 4 8 12 16 20 24 28
OVULATION
Basal body temperature
Plasma oestradiol
Plasma progesterone
Uterine endometrium
There are a number of potential ways of trying
to identify the “fertile” period..: