Components:
Female
Reproductive system
Ovary
Gwen V. Childs, Ph.D.
501- 952-5268
[email protected]
•Paired ovaries
•oviducts
•Uterus
•Vagina
•External genitalia
•Clitoris
•Labia majora
•Labia minora
•pp 461-462 Gartner/Hiatt
Components:
•Paired ovaries
•oviducts
•Uterus
•Pear shaped,
•Thick muscular
wall
•Vagina
Life Stages: Fetal Development
Oogonia develop in yolk sac (1 month)
Undergo several mitoses; migrate to
developing ovary (germinal ridge); continue
to divide to produce 5-7 million oocytes
Germinal ridge becomes cortex of ovary
Atresia
Reduces oocytes to 1 million
At birth, each ovary has 600,000 oocytes
•pp 461-462 Gartner/Hiatt
1
Fetal ovary
Surrounded by follicular
cells=primordial follicle
Neuroendocrine Regulation of Gonadotropes
Nerve cell bodies in groups
throughout the hypothalamus
produce Gonadotropin releasing
Hormone (GnRH)
Pulses of GnRH release
either LH or FSH from
gonadotropes
(basophils)
Portal veins transport the
hormones to the capillaries
of the pars distalis. Stimulate
specific pituitary cells
During Childhood
Oocytes continue to undergo atresia: At menarche, only
400,000 oocytes
Three conditions needed for puberty:
Body fat
Light
During first few hours of sleep,
Pulses of gonadotropin
releasing hormone increase.
(visionmelatonin
lower)
Gonadotrope
secrete LH
And/Or FSH
Menarche: What happens?
Peripubertal (ages 9-11)
Sleep
Ovary--Signals state of follicles
Both positive and negative feedback
First menstrual period (visible sign)
Pulses of GnRH, more regular, also during the day.
16-24%
85-104 lbs
Leptin is
permissive
Stimulates pulses of gonadotropins from pituitary
Wakes up the ovary
Slow pulses: every 1.5-3 h
FSH
Favors
follicular
development
Fast pulses:1/hour
LH
Favors ovulation
Produce gonadal steroids (estrogens)
2
Life Stages: Menopause
We ovulate 450
oocytes in a
lifetime
Remaining oocytes
Important in
hormone support.
Number of oocytes
Fetal life: 5-7 million
Women are born with all the
eggs they will have for a lifetime
Note: rapid decline
in follicles
from ages 35-45
Birth: 600,000
Menarche: 400,000
Age: 30- 100,000
Decline is more
rapid after age 35
If the decline
continued at the rate
seen at ages20-30:
We might remain fertile
well into our 70’s!
Ovary overview
Tunica albuginea
Germinal
epithelium
One layer of
squamous
follicular cells
Arrested in
Diplotene of
Meiosis I
Primordial follicle:
contains primary oocyte
cortex
medulla
Nucleus + nucleolus
3
Follicular phase: Unilaminar primary follicle
Follicular cells begin
to be cuboidal; one
layer, now called
“granulosa cells”
Primary
Oocyte
Nucleus-Also called
“germinal vesicle”
Follicular phase: Multilaminar primary follicle
Follicular phase: What causes development
to multilaminar follicle?
IGF-1 or GH??
Oocyte produces activin
Activin
stimulates
proliferation of
granulosa cells
Activin also
stimulates
pituitary FSH
secretion
Multilaminar primary follicles signal their presence to brain
and pituitary during follicular phase.
Multiple layers of granulosa cells (ZG)
Zona pellucida more prominent (ZP)
Stroma organizes:
•Theca interna (just
outside follicle)
•Theca externa outer
layer
•Develops during
follicular phase
1.Thecal cells produce androgens
2. Androgens move to granulosa
cells
Activin
stimulates
FSH
FSH
stimulates
Thecal cells
to produce LH
receptors
5. Faster GnRH pulses
3. Granulosa cells convert
androgens to estrogens
and produce activin
4. Estrogen
positive
feedback
6. More
GnRH
receptors
7. LH
rise
4
Thecal cells: Follicular
Theca externa
Secondary (antral) follicles
Theca interna
oocyte
Granulosa
cells: follicular
antrum
Granulosa cells
Follicular
phase
Pathways
Zona pellucida
What regulates Secondary follicles?
Slow pulses of GnRH
FSH stimulates:
More mature secondary follicle
Proliferation of
granulosa cells
Estrogen production by
granulosa cells (aromatase
activity)
LH receptors on thecal
cells
Cumulus
oophorous
antrum
Corona
radiata
Granulosa
cells
LH
Theca
interna
Androgen production
Inhibin production by granulosa
cells
Theca
externa
5
Ultrasound can show the
presence of antral follicles
Abnormally low
# antral follicles:
Advanced Fertility Center of Chicago
16 antral follicles
seen in this ovary
(red dots) (no
hormone treatment)
Indicates excellent
fertility
Atresia
•Ovaries small
•Only a total of 3
antral follicles
Advanced Fertility Center of Chicago
What happens to the
unused follicles?
Usually notice it as a
breakdown of oocyte
How secondary (antral) follicles signal the brain and
limit their own numbers.
Negative feedback; Inhibitory
FSH
Inhibin
Estrogens
In end, zona pellucida
may remain
+ LH and
androgens
Reduced FSH
Development of
early secondary
follicles stopped;
Some may become
atretic
6
What sets up ovulation?
Dominant Follicle (s)
About 5 follicles may become Graafian
(mature), but only 1-2 (in human) become
dominant and ovulate
Distinguishing characteristics of dominant
follicle: Size! And, look at follicular fluid
Early in cycle, estrogen from
granulosa cells exert positive
feedback on brain & pituitary
Rapid
GnRH
pulses
1/hour
Increase
GnRH
receptors
LH pulses
increase to
a surge
More inhibin!
Estrogen:androgen >1
Conditions not good for FSH secretion
What does LH surge do?
1. Stimulates
meiosis inducing
factor
Stimulates oocyte
to complete meiotic
prophase; Now a
secondary oocyte
2. Stimulates
plasminogen
activating factor
Converts proenzymes
for plasmin and
collagenase to mature
enzymes
3. Inhibits inhibin
Breaks down
connective
tissue to
release egg
Permits a midcycle rise in FSH
1. Oocyte completion of meiosis
Germinal vesicle breakdown: (GVBD=nuclear
membrane breakdown to allow completion of meiotic
prophase and meiosis I)
Unequal division produces polar body, which rides along
with oocyte during ovulation, stuck to zona pellucida
Oocyte is now a secondary oocyte
Chromosomes assemble on metaphase plate; arrested at
this point until after ovulation and fertilization.
Protects and stimulates future secondary follicles
7
Lawrence L Espey, Trinity Univ. San Antonio, TX
10 hours before ovulation
30 min--1 hour before ovulation
2. Before ovulation, Oocyte faces the above layers
Ovulation
• Fluid buildup and reorganization of follicle
so that oocyte and granulosa cells (corona
radiata) are free in fluid
• Bulge against wall of ovary, pale because
vessels in theca have withdrawn. (stigma
or macula pellucida)
• After breakdown of connective tissue by
enzymes, oocyte and fluid are released to
be picked up by oviduct.
• Remaining follicle collapses on itself.
Layers 1-5 min before ovulation
Route of the oocyte
Lawrence L Espey, Trinity Univ. San
Antonio, TX
Images of human oocytes
Immature
Note: nucleus
(GV) intact
Advanced Fertility Center of Chicago
8
Corpus hemorrhagicum: after ovulation
Luteal Phase: Corpus luteum
LH
Luteinization of granulosa and thecal cells
Both cell types
secrete
progesterone
clot
•Follicle collapses
•Theca and granulosa cells intermingle
•blood from capillaries in theca forms a clot in center
Corpus luteum
Theca cells secrete
androgens and
granulosa cells
convert to estrogens
Stimulates and maintains uterine lining
Maintenance of Corpus luteum (CL)
LH surge starts it off
Must be maintained by
feedback from the placenta
(chorionic gonadotropin
Theca (small, dark); +
granulosa cells
(large, foamy and
more numerous)
Its secretion of progesterone
and estrogen shut off
pituitary gonadotropins
(negative feedback)
No pregnancy, no gonadotropic
maintenance. CL atrophies in about 14-16
days; progesterone and estrogen levels fall.
Fall in progesterone and estrogen stimulate rise in FSH
early in the next cycle
9
Corpus albicans = remnant of corpus luteum after
it undergoes apoptosis
Review:
GnRH pulses
slower
GnRH
pulses
faster
LH surge
GnRH
pulses
slower
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