Female Reproductive

System Physiology

Suyasning HI
 Lecture Outline

The Basics
Gametogenesis
Gender determination
The Pituitary-Gonad Axis
Female Reproductive Physiology
Ovarian Cycle
Uterine Cycle
Hormonal control and changes
 The Hypothalamus

The hypothalamus is located at the base of the forebrain and regulates homeostatis:
metabolic/autonomic activities such as food intake, energy expenditure, body weight, fluid
. intake and balance, thirst, blood pressure, body temperature, sleep cycle, and reproduction
 The Pituitary Gland

The pituitary gland, or hypophysis, the size of a pea sits in a

small, bony cavity (sella turcica) at the base of the brain and is
functionally connected to the hypothalamus
Hypothalamus releases hormones into the pituitary (including
GnRH)

The posterior pituitary lobe (neurohypophysis) is directly connected to the brain and is
. derived from the neural ectoderm

The anterior (adenohypophysis) and intermediate lobes are derived from the oral ectoderm

FYI: In humans the intermediate lobe is a thin layer of cells between the anterior and )
(posterior lobes
GnRH neurons Structure
of the
median
eminence

GnRH neurons

Figure 6
GnRH acts on pituitary to release LH and
FSH
Hypothalamic-Pituitary-Gonadal Axis
HPG-Axis
HYPOTHALAMIC-PITUITARY-GONADAL
AXIS

Hypothalamus Feedback by
:Steroid Hormones

GnRH Estrogen
Produced by granulosa cells/developing
follicles
Progesterone
Anterior Pituitary secreted from the developing corpora lutea
(Testosterone)

FSH & LH Negative or Positive Feedback

Gonads
Anatomy of
 GnRH
Feedback Regulation

LH pulse/60 mins 1 LH pulse/90 mins 1

 : Early in Follicular Phase
Estradiol is secreted by developing follicles, therefore estradiol is low. Correspondingly, there is a
weak estradiol-induced inhibition of the GnRH pulse generator and LH pulse frequency is relatively
. fast at 1 pulse/60 mins

LH pulse/60 mins 1 LH pulse/90 mins 1

 : Late Follicular Phase
As estradiol level builds up as follicular phase progresses, a stronger negative estradiol-
induced regulatory feedback on the GnRH pulse generator is observed leading to a
reduced LH pulse frequency of 1 pulse/90 mins

LH pulse/90 mins 1
 : Preovulatory GnRH/LH-Surge
However, as more estradiol is produced (see pre-ovulatory peak), a level is achieved
that leads to a positive estradiol-induced feedback on the GnRH pulse generator
and the surge release of LH and FSH and ovum release
 : The luteal phase
the empty follicle transformed into the corpus luteum. This becomes a rich source of progesterone
(and some estradiol). This maintains pregnancy and together strongly negatively feeds back on the
.GnRH pulse generator
Regulation of GnRH neurons
Much research is ongoing
to further delineate the
functional network that
controls GnRH neurons
Numerous neuro-
transmitters and
peptides have been
identified to regulate
GnRH )>35(
Kisspeptin is a major
modulator
 Steroids act during different times of life

:Steroid feedback of GnRH secretion in adulthood

Activational effects

Steroids act on GnRH system during puberty

Steroids act during early/prenatal life

Organizational effects: cause permanent changes
to reproductive )and other systems(
Steroid Feedback on GnRH neurons

GnRH neurons lack receptors for estradiol )ER

; alpha( and progesterone
some contain ER beta, but this receptor is not
involved with estradiol-feedback on GnRH
neurons
So, steroids provide feedback on GnRH system
indirectly via interneurons
SEXUAL DIMORPHISM OF
BRAIN
 DIFFERENTIATION OF THE BRAIN:
THE ACTIVE AGENT IS ESTRADIOL
Testosterone is converted to estradiol once it has
entered the relevant neurons )enzyme that converts
. testosterone to estradiol: aromatase(
Thus, it is estradiol/estrogen that acts inside neurons to
stimulate sexually dimorphic patterns of neuronal
circuitry as a result of the presence of testosterone in
.developing males
Organizational effects of estradiol
Humans: prenatal
Essential female reproductive System
:functions

1-oogenesis

6-lactation 2-reception
Of baby Of sperms

Female
Reproductive
functions

3-transport
5-give birth Of sperms
)parturition( &
ova

4-pregnancy
)maintain
Growing fetus(
 Functional Comparison Between Male &
Female reproductive systems

Male-1 Female-2
A-Pair of A-Pair of
gonads=Testes gonads=Ovaries

B-Produce gametes B-Produce gametes

)sperms( +sex Sex hormones(+ ova)
hormones )estrogen-progesterone(
)testosterone(
Sexual cycle in female

:Same as male sexual cycle )4 phases(

Sexual
cycle

1-excitation 2-plateau 3-orgasm 4-resolution

 Feedback loops and targets organs in the
.hypothalamic-pituitary-ovarian axis

The hypothalamic GnRH secretion shows a cyclic variation in adult

females of approximately 28 days, probably a genetic code imposed
.by the CNS

Peaks of GnRH release reach the adenohypophysis through the. 1

portal system, and release both FSH and LH to reach the ovary via
.the systemic circulation

FSH stimulates follicular growth, inhibin-release from stromal. 2

cells, and aromatase activity in the ovary. Aromatase converts
.androgens to oestrogens

.LH stimulates the ovarian androgen production. 3

Inhibin is the primary inhibitor of FSH release by blocking the . 4

.effects of GnRH on the adenohypophysis
Dual & interrelated ovarian
:functions
Ovaries:

1-Oogenesis 2-Secretion of female sex hormones

i.e produce ova i.e. estrogen & progesterone
Menstruation )Menstrual cycle(:
The menarche is the age at the first menstrual
bleeding. It often occurs between the 12th and
the 14th year.

A normal bleeding corresponds to a loss of up

to 50 ml of whole blood. The mixture of vaginal
fluid and menstrual blood produces a pH close
to that of normal blood. The average cycle
length is 28 days.
 Menstrual cycle Phases
1-Proliferative Phase
Menstrual Cycle Start: after menstruation
ends: before ovulation
Duration: 9 days
Produced by: estrogen
Coincide: with follicular phase
Changes: ++endometrial thickness
Glands increase in length
)but dont secrete
2-Secretory phase:
Starts: after ovulation
Ends: before menstruation
Duration: 14 days
Coincide; CL formation
Changes: estrogen & progesterone
More increase endometrium Thickness &fat,glycogen
Deposit in cells)=decidual cells(
Gland totuous )curl(, secrete fluid

3-Destructive phase
)Bleeding or menstrual(
Occur only if ovum not fertilized
Duration: 3-5 days
Cause: degeneration of CL_____---estrogen&progesterone
Endoetrium :thinner,foci of necrosis appear
++local prostaglandins____V.C___sloughing of
Superficial layers of endometrium____menstrual blood flow
 Female Reproductive Physiology
The Cycles

Hormonal
control of
the ovarian
cycle
 Female
Reproductive
Physiology
All together
 Ovarian Cycle Phases
Ovarian Cycle

3-Luteal Phase
1-Follicular Phase
2-Ovulation LH__+proliferation of cells
A-FSH+++several
Of ruptured follicle___CL
primordial follicles
)cells are yellowish lipid rich(
Near midcycle)day 14( [Corpus Luteum]
B-One mature
++++Estrogen excess__+ve
To become Graafian
Feedback____LH surge Corpus luteum secrete
Follicle)maturation
++Estroegn & Progesterone
Need LH also(
LH surge___ovulation __-ve feedback___--LH__
) 9 hours after LH peak( This leads to CL degeneration
C-Follicles secrete
___---estrogen& progesterone
Estrogen & inhibin
__++FSH&LH and new cycle
 ?Fate of corpus luteum
1-If fertilization of the released ovum takes place____it
prepares the endometrium for the implantation of the
fertilized ovum )continue to secret estrogen &
progesterone (

2-if no fertilization occur___it degenerates

Which leads to loss of hormonal support to the uterine
lining__disintigration & sloughing____)menstrual blood
flow(

Then the cycle restarted by the follicular phase again to*

rebuild the endometrium )under effect of estrogen(
 For some women, there can be a few simple physical indications that
they are at the day of ovulation:-

1-Some women feel a light tension in the breasts.

2-Sometimes a little pain can be felt at the left or right ovary.

The cervical mucus becomes much more abundant )usually the 10th to 14th day in a normal 28 day-3
. cycle(. This creates an ideal medium for the spermatozoa to swim in

4-There are two much more accurate methods of knowing the date of ovulation:

A-The temperature method:

At the day of ovulation, the temperature increases to the region of 37.2 to 37.3.

B-The testing method:

The second method to know the day of ovulation is a simple ovulation test that can be found at your local
pharmacy.
This test measures the level of the LH hormone )Leutenising Hormone( in the urine. It is normally advised
that this test be taken each day from the 11th day of the cycle
This is a very reliable test and gives about 98% accuracy for the date of ovulation.
 :Cyclic changes in Cervix, vagina & breasts

Cervix-1 Vagina-2 Breasts-3

Estrogen:make mucus Estrogen:cornification Estrogen:Proliferation
Thinner,more alkaline If of vaginal epithelium of breasts ducts
spread on slide__dries
in fern like manner

Progesterone:make Progesterone:thick Progesterone:growth

mucus mucus of breast lobules &
thick,tenaciuous,more secretion,proliferation alveoli
cellular,If spread on of vaginal epithelium
slide__doesnt fern and leucocytes
infiltration
 Estrogen &
Progesteron Lihat tabel siklus menstruasi

:Estrogen
Penebalan epitel vagina
Mitosis and siliogenesis di tuba tubal
Silio-microvillogenesis & proliverasi endometrial
Perkembangan stroma dan duktus, pembentukan
jaringan lemak di kelenjar mammae
Meningkatkan akivitas osteoblas
Deposit lemak tubuh

Female Reproductive System 40

Estrogen dan progesteron
:Progesteron
Fase Sekretori endometrium
Menurunkan kontraksi uterus
Meningkatkan pergerakan silia di tuba
Proliferasi alveolar dan sekresi kelenjar
mammae
Deposit glikogen
Edema Stroma

Female Reproductive System 41

:Fertilization & implantation

2-Fertilized ovum
divide mitotically

1-Union of Sperm + Ovum ___become blastocyst

Occur in oviduct

4- Enzymes of blastocyst: 3-Blastocyst implants

)enzymes help(into preprepared
Create a hole in endometrium
+release glycogen Endometrium)very vascular
+rich in glycogen(
 :Fertilization & Implantation
1-Site: Fertilization occur at mid portion of fallopian
tube,sperms become more able of fertilization after
their journey in female genital tract )sperm capacitation(
2-Method Sperm bind to zona pellucida followed by acrosomal
reaction)i.e. breakdown of acrosome and release of
enzymes as acrosin )trypsin like protease( which
facilitate penetration
Polyspermy )penetration of ovum by more than one
sperm is prevented by fusion of sperm with zona
pellucida causing structural changes in it(

3-Zygote Formed from fusion of sperm&ovum

4-Blastocyst: Formed due to mitotic division of the zygote
5- Occurs about 6-7 days after fertilization
Implantation )blstocyst reaches the uterus within 3 days,remains for
another 3 days( during this period the endometrium is
prepared by progesterone from CL
The outer layer )syncytiotrophoblast erodes the
 :Methods of contraception
Contraception

1-Rhythm method:
)safe period(
3-Contraceptive pills
2-IUDs)Intruterine devices(
)hormonal method(
Avoid intercourse
During fertile period
)120 hours=5 days(
Pills contain,
Ovum survive 72 hours
Large doses of estrogen alone
Sperm survive 48 hours
Or combined with progesterone

Mechanism of action:inhibit FSH

So safe period= Idea:place a foreign body
&LH release
before day 9 i.e.)a loop( in the uterus
after day 20 Which prevents implantation
Also progesterone makes
Of the fertilized ovum
Cervical mucus thick
Not safe 100%
And not easy for sperm
As ova& sperms may
Penetration
Live for longer time More effective method
And cycles length
Effective method
are not
all same in all women
 :Hormonal control of the Breasts
1-Estrogen: Causes proliferation of the ducts,development
of the nipples and increase fat deposition
2-Progesterone: Causes growth of the lobules & alveoli
3-Prolactin: Causes milk formation and secretion
Together with estrogen,progesteron,hCS
produce full lobuloalveolar development of
breasts during pregnancy
4-Oxytocin: Causes milk ejection)milk let down(
Its secretion is stimulated by breast suckling
and also affected by conditioned
reflexes)mothers hearing their baby cry__milk
secretion(
5-Other Insulin,glucocorticoids,growth hormone
hormones: needed for breast response to other
hormones.thyroid hormones are also
necessary for milk secretion
 :Functions and regulation of prolactin hormone
:Functions of prolactin :Regulation of prolactin
1-Causes milk secretion from 1-Suckling reflexly stimulate prolactin )and
breasts prepared 1st by Oxytocin( secretion
estrogen & progesterone
2-Shares other hormones in 2-estrogen increase prolactin secretion
full breasts development during pregnancy but antagonizes its milk
during pregnancy producing effect)so inhibit lactation during
pregnancy(
3-causes amenorrheoa 3-PIH )prolactin inhibitory
during lactation)as it inhibits hormone=dopamine(secreted from
GnRH secretion and hypothalamus inhibit prolactin secretion,so
antagonizes the action of L-dopa decrease prolactin secretion,while
FSH&LH on the ovaries( serotonin increase prolactin secretion
Prolactin increase relaese of PIH___so
inhibit its own secretion)-ve feedback(

4-Sleep,exercise ,surgical & psychological

stresses increase prolactn secretion
Suckling reflex for lactation

2-Oxytocin causes the contraction

1-Suckling triggers Of myoepithelial cells that surround
The release of oxytocin The alveoli squeez milkout into ducts
+ prolactin __milk ejection

3-Prolactin help
Resynthesis
Of milk to replace
The used milk by the baby
 :Functions of estrogen and Progesterone
Estrogen
1-Facilitate growth of follicles
2-growth of female external genitalia,breasts duct
system
3-Produce female 2ry sex characters,body
configuration,fat distribution & increase libido
4-Produce proliferative phase of
Menstrual cycle,++uterine blood flow,musculature
and make it more sensitive to oxytocin
5-produce cyclic changes in cervix & vagina
6-Control FSH&LH secretion & causes the LH
surge at midcycle
7-Has metabolic anabolic effects, cause
epiphyseal closure of bones)also ++bone
density(,decrease serum cholesterol level,+
+angiotensinogen secretion from liver,increase
HDL,--LDL)Cardioprotective(
Produce salt & water retention
Progesterone
1-Causes secretory phase of menstrual cycle
2-Stimulate developmentof breast lobules &
alveoli
3-Essentia for maitenance of pregnancy
4-Decrease sensitivity of uterus to oxytocin
5-Produce cyclic changes in cervix & vagina
6-Inhibit LH secretion during pregnancy
)producing amenorrhea(
7-Thermogenic effect)++body temperature by
0.5 C at ovulation(
++respiratory rate___---alveolar CO2
Produce natriuresis
No anabolic functions
:Functions of the Placenta
1-Nutritional
Function
)vitamins&nutrients
From mother to fetus(

5-Protective function
Effective barrier
2-RespiratoryFunction
Prevent passage of
O2 from mother to fetus
Toxins,bacteria to fetus
CO2 from fetus to mother
&Transfer antibodies
From mother to fetus
Placenta

4-Secretory function
)edocrine function(
3-Excretory function
hCG,EstrogenProgesterone
Of Fetal waste products
Relaxin,hCS,TSH
B endorphin,GnRH,inhibin
 ?What is Menopause

months of amenorrhea )no menses( 12

Average age 51
Derived from the Greek words men )month(
and pausis )cessation(
Primary ovarian function stops
Marks the permanent end of fertility
 Perimenopause

Transition
Change from normal ovulatory cycles to
complete cessation of menses
Marked by menstrual irregularity
May begin years prior to menopause
Onset of menopausal symptoms
 Changes in Hormone Patterns
Inhibin levels fall
Produced by granulosa cells
Decrease may be from declining number of follicles or
reduced quality/capacity of aging follicles Speroff
Serum FSH levels rise
Slight increase in estradiol levels
 Changes in Hormone Patterns

Cycle variability increases

Hormone levels fluctuate
FSH and estradiol may return to premenopausal
ranges
After menopause, ovary no longer secretes
estradiol continues to produce androgens
)under continued stimulation of LH(
Elevated levels of FSH and LH = evidence of
ovarian failure
Thank you