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Chapter 2 Physiology Of

Reproduction In Women
Women's life can be divided into seven
stages according to their physiological
characteristics
Different periods of Female

fetal period
Neonatal period : 4 weeks
childhood: 4 weeks to age of 12
Adolescence or Puberty
sexual maturity: maintains for 30 years
peri-menopausal period:begain 40, the short
1-2 years long maintains for 10-20 years
senility
fetal period

The combination of sperm and ovum


is the beginning of a new
life.Sex chromosomes include X
chromosome and Y chromosome
XX zygote were female XY
zygote were male, female sex
organs by two Mullerian formed. At
the beginning of embryo at 6 week,
the primordial gonads began to
differentiate, if the absence of Y
chromosome, and the appearance of
ovarian tissue in 8-10 weeks
childhood

Later (8 years old)


the state of GnRH inhibited are releasing, the
follicle by the pituitary gonadotropin began to a
certain degree of development , and secretion of
sex hormones, but not mature.
Breast also began to develop, began to show
female characteristics
PUBERTY AND MENOPAUSE

PUBERTY(adolescence)
Defination
Puberty is the period when the endocrine and
gametogenic functions of the gonads first
develop to the point where reproduction is
possible.
PUBERTY AND MENOPAUSE

PUBERTY
Events
1.Thelarche: 10 years of age began to appear breast
development (E,P)
2.Adrenarche: an increase in the secretion of adrenal
androgens. Pubarche: the development of axillary and pubic
hair.(A)
3.Menarche: the first menstrual period.
4.growth spurt 11-12
years 9cm/years
PUBERTY AND MENOPAUSE

Age: from 8-13 years old WHO 10-


19
Control Of Onset Of Puberty
A neural mechanism is responsible for the
onset of puberty .
PUBERTY AND MENOPAUSE

Sexual Precocity
Precocious pseudopuberty :
the precocious sexual development in humans is
caused by exposure of immature males to androgen
or females to estrogen.
True precocious puberty:

it due to an early but otherwise normal puberty


pattern of gonadotropin secretion from the pituitary.
PUBERTY AND MENOPAUSE

Sexual Precocity
Precocious puberty,
The most frequent endocrine symptom of
hypothalamic disease.
Lesions of the ventral hypothalamus near the
infundibulum.
Interruption of neural pathways that produce inhibition
of the GnRH pulse generator.
Chronic stimulation of GnRH secretion.
PUBERTY AND MENOPAUSE

Delayed Or Absent Puberty


Defination:
The normal variation in the age at which adolescent changes
occur is so wide that puberty cannot be considerered to be
pathologically until menarche has failed to occur by the age of
17.

Reasons panhypopituitarism (dwarfing+endocrin


abnormalities)
In some individuals,puberty is delayed,even though
the gonads are present and other endocrine functions are
normal.
sexual maturity

Beginning from 18 years old, and lasting 30 years. Ovarian


function is mature, periodic ovulation and periodic
menstruation. Reproductive organs and breasts occur cyclical
changes by the ovary secretion sex hormones
PUBERTY AND MENOPAUSE

MENOPAUSE
conception:
The human ovary gradually becomes unresponsive to
gonadotropins with advancing age, and its function declines, so
that sexual cycles and menstruation disappear.

Age:
In women, the menses usually become irregular and cease
between the age of 45 and 55.
PUBERTY AND MENOPAUSE

MENOPAUSE
Age:the menses usually become irregular and cease between
the ages of 45and 55.
Hormones levels:
The ovaries no longer secrete progestrone an 17-estrodiol in
appreciable quantities. As the negative feedback effect of the
estrogens and progestrone is reduced, secretion of FSH and
LH is increased, and plasma FSH and LH rise to a high level.
Symptoms:
1.The uterus and vagina gradually become atrophic.
2.Sensations of warmth spreading from the trunk to the face(hot
flash), night sweats, and various psychic symptoms.
MENSTRUATION AND THE CLINICAL
FINDINGS IN THE MENSTRUAL PHASE

MENSTRUAL CYCLE
Conspicuous feature:
The periodic vaginal bleeding that occures with the
shedding of the uterine mucosa.

The length of the cycle:


Notoriously variable.
But an average interval between two periods is 28
days from the start of one menstrual period to the starts
of the next.
MENSTRUATION AND THE CLINICAL
FINDINGS IN THE MENSTRUAL PHASE

NORMAL MENSTRUATION
The origin of menstrual blood :
predominantly arterial.
Composition: tissue debris cervical mucus,vaginal
epithelial cells.
prostaglandins fibrinolysin unclot .
Duration of the menstrual cycle:
1to 8 days (3-5days).
The amount of lost blood:
Less than 80ml (30ml).
MENSTRUATION AND THE CLINICAL
FINDINGS IN THE MENSTRUAL PHASE

ANOVULATORY CYCLES
Time:
The first 12-18 months after menarche.
Before the onset of menopause.
MENSTRUATION AND THE CLINICAL
FINDINGS IN THE MENSTRUAL

PHASE

ANOVULATORY
CYCLES
Preceeding:
Ovarian function

Ovarian function
producing ova ovulation for
reproductive function

secretion ovarian hormones for


endocrine function
CONTROL OF THE MENSTRUAL CYCLE

OVARIAN CYCLE
From the time of birth,there are many
primordial follicles under the ovarian capsule.
Each contains an immature ovum.
The periodic changes in ovaries
Cyclical changes in the
ovary

From puberty to menopause Ovarian recurrence


Cyclical changes in morphology and function of the
ovary
Embryo 6-8 weeks 600 thousand oogonia
Embryo 11-12 weeks First meiotic division
Primary oocyte
Embryo 16-20 weeks 6-7 million oogonia1/3 The
rest are primary oocytes
At birth 2 million
puberty 300 thousand
Development and
maturation of follicle
There are about 2 million follicles
in the ovary at birth Majority
follicle degeneration Degraded
follicles are called atresia
follicles There are only 300
thousand left during puberty
Women in life generally only 400-500
follicles mature Roughly through
the following four processes
Development and maturation of
follicle

1 primordial follicle
2 preantral follicle
3 Antral follicle
4 preovulatory follicle


primordial follicle

Primordial germ cells are called


oogonium after mitosis oogonium are
called primary oocyte after the first
meiosis and arrest in the meiosis
diplotene stage
primordial follicle is Basic unit of
reproduction is also the only form of
ovarian reserve
preantral follicle

Flattened granule cells were transformed into single


cuboidal cells ,primordial folicle were divided into
primary follicles
Layers of granulosa cells reach to 6-8 layers ,becomes
secondary follicles
At this stage, granulosa cells appear the three receptors,
which is necessary on the follicle growth and development,
follicular stimulation (FSH), estradiol (E2) and
testosterone.

follicle have the ability to synthesize sex hormones


Antral follicle

under the influence of the estrogen and follicle


stimulating hormone (FSH) produce follicular
fluid, form follicular cavity. Under the action of
FSH, the granulosa cells of this period exsist
luteinizing hormone (LH) receptor, and under the
action of LH, estrogen production increased
significantly receptor.
preovulatory follicle

For the final stage of follicular development,


follicular fluid increased, follicular cavity
increased, up to 1-2cm in diameter, said mature
follicles
CONTROL OF THE MENSTRUAL CYCLE

OVARIAN CYCLE
Proceeding Of The Cycle
Start :several of these follicles enlarge and carvity forms around the ovum.
The sixth day: one of the follicles becomes the dominant follicle, the others regress (atretic follicles).
the follicle secretes estrogens

The 14th day: the distended follicle ruptures, and the ovum is extruded into the abdominal cavity
(ovulation).
Ovum ----oviducts--------uterus--------degenerates or out of the vagina.
The follicle that ruptures promptly fills with blood. The granulosa and theca cells of the follicle
lining promptly begin to proliferate,and the clotted blood is rapidly replaced with yellowish, lipid-
rich luteal cell,forming the corpus luteum( .
the luteal cells secret estrogens and progesterone

Pregnancy --------corpus luteum persists, no more menstrual periods until after delivery.
The 24th day: No pregnancy--------- corpus luteum begins to degenerated ,and eventually replaced
by fibrous tissue, forming a corpus albicans.
3. Formation and
degeneration of corpus
luteum
Ovarian follicular fluid outflow Decreased follicular cavity
pressure The follicle wall collapse, forming many folds
Follicular granulosa cells and theca cells of the follicle invade
inward formed corpus luteum Growth of the corpus luteum
depends on its developing an adequate blood supply, and there
is evidence that vascular endothelial growth factor (VEGF) is
essential for this process. If pregnancy occurs, the corpus
luteum persists, and there are usually no more menstrual
periods until after delivery If there is no pregnancy, the
corpus luteum begins to degenerate about 4 days before the
next menses ( day 24 of the cycle ) and is eventually replaced by
fibrous tissue, forming a corpus albicans After Corpus luteum
function decline begin new cycle
Proceeding Of The Cycle corpus luteum persists, no
more menstrual periods until
Ovum ----oviducts----uterus---- after delivery.
degenerates or out of the vagina.

Pregnancy
ovulation
The follicular phase The luteum phase
Start The 6th day No pregnancy
The 14th day The 24th day
several these one
several of these oneofof the
the follicles
follicles
follicles
follicles enlarge
enlarge becomes
becomes the the the distended follicle corpus luteum begins to
and
and carvity
carvity dominant
dominant follicle,
follicle, ruptures, and the ovum is
extruded into the degenerated ,and eventually
forms around the
forms around the others
others regress
regress abdominal cavity replaced by fibrous tissue,
the
the ovum.
ovum. forming a corpus albicans.
follicular fluid theca interna
granulosa cells

Maturity follicle
In humans, no new ova are formed after
birth. During fetal development , the ovaries
contain over 7 million germ cells; however,
many undergo involution before birth, and
others are lost after birth. At the time of birth,
there are approximately 2 million primordial
follicles containing ova, but approximately
50% of these are atretic.
OVARIAN CYCLE

atresia
continues
the million or so ova undergo
the first part of the first meiotic
Involutes division and enter a stage
before birth of arrest before adulthood.

there are approximately


the ovaries contains 2 million primordial the number of ova is
over 7 million germ follicles containing ova, less than 300,000
cells 50% of these are atretic

the remainder
degenerated

normally, only one of these


ova per cycle (about 500)is
stimulated to mature

Fetal development At the time of birth At the time of puberty


CONTROL OF THE MENSTRUAL CYCLE
Ovum

OVARIAN CYCLE

1.Before ovulation, the first meiotic Primordial oocyte
division is completed.

2.The secondary oocyte receives most


of the cytoplasm, the first polar body
fragments and disappears. Polar
Body
3.The secondary oocyte begins the
second meiotic division but stops at
metaphase and is completed only
when a sperm penetrates the
oocyte. ovum

4.At that time, the second polar body is


cast off and the fertilized ovum Secondary oocyte
proceeds to form a new individual.
CONTROL OF OVARIAN
FUNCTION
Hypothalamic Hormones
These substances are produced by
neurons and enter the portal hypophysial
vessels,a special group of blood vessels that
transmit substances directly from the
hypothalamus to the anterior pituitary gland.
CONTROL OF OVARIAN
FUNCTION
Hypothalamic Hormones
The hypothalamus occupies a key role in
the control of gonadotropin secretion exerted
by GnRH. GnRH stimulates the secretion of
FSH and LH.

fashion of secretion: episodic fashion


CONTROL OF OVARIAN
FUNCTION
PituitaryHormones
Ovarian secretion depends on the action of
hormones secreted by the anterior pituitary
gland.
There are 6 established hormones:
ACTH GH TSH FSH LH LPH.
CONTROL OF OVARIAN
FUNCTION
Pituitary Hormones
1.Gonadotropins (FSH LH)
FSH LH

Composition andsubunits andsubunits

The half-life 170 minutes 60minutes


time

Effection FSH is responsible for early 1. LH is responsible for final follicle


maturation of the ovarian maturation with FSH.
follicles and for final follicle 2. A burst of LH secretion triggers
maturation with LH. ovulation and the initial formation of
the corpus luteum.
3. LH stimulates the secretion of estrogen
and progestrogen from the corpus
luteum.
CONTROL OF OVARIAN
FUNCTION
Pituitary Hormones
2.Prolactin
Prolactin causes milk secretion from breast
after estrogen and progestrone priming.
Feedback Effects

GnRH Hypothalamus

Anterior Pituitary
LH FSH

Estrogen Inhibin B

Estrogenic
Theca interna Granulosa Ovary
effects

Androgens
Feedback Effects

1. LH regulates thecal cells ( E ) .


2. Both LH and FSH regulate the granulosa
cells.
Feedback Effects

It should be emphasized
that a moderate, constant
level of circulating Estrogen
exerts a negative feedback
effect on LH secretion,
whereas an elevated
Estrogen level exerts a
positive feedback effect and
stimulates LH secretion.
When circulating levels of
Progesterone were high, the
positive feedback effect of
Estrogen was inhibited.
Feedback Effects

At the start of the follicular phase: Fostering follicular growth.


( inhibin B is low ; FSH is elevated ; LH is held in check by E)

At 36-48 hours before ovulation :


the E feedback effect becomes positive to initiate the burst of LH secretion
that produces ovulation.

ovulation occurs :
9 hours After the LH peak:.(FSH also peaks, despite a small rise in inhibin B)

During the luteal phase:


the secretion of LH and FSH is low, because of the elevated levels of E ,P ,
and inhibin B.
Control of Menstrual cycle

Inan important sense, regression of the


corpus luteum (luteolysis) starting 3-4 days
before menses is the key to the menstrual
cycle.
the combined action of PGF2a and ET-1 can
regression of the corpus luteum .
luteolysis begins
---the E and P levels fall and the secretion of FSH and LH increases
--- a new crop of follicles develops
--- a single dominant follicle matures( FSH and LH) Near midcycle,
--- a rise in estrogen secretion from the follicle.
(This rise augments the responsiveness of the pituitary to GnRH and triggers a
burst of LH secretion.)
---ovluation
---the formation of a corpus luteum.
(There is a drop in estrogen secretion, but progesterone and estrogen levels then
rise together, along with inhibin B. )
---The elevated levels of E and P inhibit FSH and LH secretion for a while, but
luteolysis again occurs and a new cycle starts.
The cyclic changes in the
endometium and other genital
organs during the menstrual cycle
uterine cycle
uterine cervix cycle
vaginal cycle
the cycle of breasts
indicators of ovulation
UTERINE CYCLE

By the end of each menstrual period,all but


the deep layer of the endometrium has
sloughed.
under the influence of E from the developing
follicles, the endometrium regenerates from
the deep layer and increases rapidly in
thickness.
UTERINE CYCLE

The superficial two-thirds of the


endometrium is shed during
menstruation.It is supplied by
The stratum long,coiled spiral arteries.
Endometrium functionale

It is supplied by short, straight


basilar arteries, is not shed during
The stratum menstruation.
basale
UTERINE CYCLE

Under the influence of estrogens from the


developing follicles,the endometrium
regenerates from the deep layer and
increases rapidly in thinkness during the
period from the 5th to 16th days of the
menstrual cycle.
the proliferative phase---- preovulatory
---follicular phase of the cycle.
UTERINE CYCLE

After ovulation,the endometrium becomes


more highly vascularized and slightly
edematous from the corpus luteum.
the secretory or luteal phase.
the preparation for implantation of the fertilized
ovum.
when the fertilization fails to occur during the
secretory phase,the endometrium is shed,and
a new cycle starts.
UTERINE CYCLE

the proliferative phase


- the restoration of the epithelium from the
preceding menstruation,
the secretory phase

- the preparation of the uterus for


implantation of the fertilized ovum.
UTERINE CYCLE

Thelength of the secretory phase is


remarkably constant, at about 14 days,
The variations seen in the length of the
menstrual cycle are due to variations in the
length of the proliferative phase.
CYCLIC CHANGES IN THE
UTERINE CERVIX
estrogen

makes the mucus thinner and more alkaline.


progesterone

makes the mucus thick ,tenacious,and


celluar.
CYCLIC CHANGES IN THE UTERINE
CERVIX
At the time of ovulation:
The mucus is thinnest, and its elasticity or
spinnbarkeit increases ( 8-12 cm or more in length ).
It dries in an arborizing, fernlike pattern when a thin
layer is spread on a slide.
After ovulation and during pregnancy:
The mucus becomes thick and fails to form the
fern pattern.
CYCLIC CHANGES IN THE UTERINE
CERVIX

The arborizing,
fernlike pattern
VAGINAL CYCLE

estrogens

make the vaginal epithelium becom


cornified
progesterones

make the thick mucus is secreted ;


make the epithelium proliferates and become
infiltrated with leukocytes.
CYCLIC CHANGES IN THE
BREASTS

Estrogens
cause proliferation of mammary ducts.
Progesterones
cause growth of lobules and alveoli.
CYCLIC CHANGES IN THE
BREASTS

breast swelling,tenderness,and pain

distention of ducts,
hyperemia,
edema of the interstitial tissue of the breasts
indicators of ovulation
Knowing when during the menstrual cycle ovulation occurs
is important in increasing fertility or conversely, in
contraception.

There are two indicators of the time of ovulation:


One is a rise in the basal body temperature
thermometer
( probably due to P---thermogenic ).

The other one is a rise in urinary LH (ovulation normally


occurs about 9 hours after the peak of the LH surge).
NDICATORS OF OVULATION

The ovum lives approximately 72 hours after it is


extruded from the follicle, but is probably fertilizable for
less than half this time.
And some sperms can survive in the female genital
tract and produce fertilization for up to 120 hours before
ovulation, but the most fertile period is clearly the 48
hours before ovulation.
SEXUAL HORMONES

ESTROGENS
Secretion Of Estrogens
Almost all of the estrogen comes from the
ovary. There are 2 peaks of secretion: one
just before ovulation (follicle)and one during
the midluteal phase(corpus luteum). After
menopause, estrogen secretion declines to
low levels.
SEXUAL HORMONES
ESTROGENS

1 Effects On Female Genitalia


their role in the cyclic changes in the
endometrium,cervix,and vagina is discussed
above.
estrogens facilitate the growth of the
ovarian follicles and increase the motility of
the uterine tubes.
ESTROGENS

2 Effects On Endocrine Organs


E decreases FSH secretion.
In some circumstances, E inhibits LH
secretion ( negative feedback ), and in others, it
increases LH secretion ( positive feedback ).
E also increases the size of the pituitary.
E cause increased secretion of angio-
tensinogen and thyroid-binding globulin.
ESTROGENS

3 Effect On The Breasts


E produces ducts growth in the breasts
and are largely responsible for breast
enlargement at puberty in girls.
ESTROGENS

4 Effect On Female Secondary Sex Characteristics

1. The body changes that development in girls at puberty are due


to E (and absence of A).
2.women have narrow shoulders and broad hips, thighs that
converge, and arms that diverge, this body configuration, plus
the female distribution of fat in the breasts and buttocks are due
to E (and absence of A).
3. In women, the larynx retains its prepubertal proportions and the
voice is high-pitched. There is less body hair and more scalp
hair, and the pubic hair generally has a characteristic flattop
pattern. All of them are due to E.
ESTROGENS

5 Other Actions Of Estrogens


1.E can cause some degree of salt and water retein.
2.E makes sebaceous gland secretions more fluid and thus to counter
the effect of testosterone and inhibit formation of comedones and acne.
3. E has a significant plasma cholesterol-lowering action and they
produce vasodilation and inhibit vascular smooth muscle proliferation
(NO).
4. E presents expression of factors important in the initiation of
atherosclerosis.
5. the liver palms, spider angiomas, and slight breast enlargement in
advanced liver disease ( E ).
6. Estrogens are responsible for estrus behavior in animals, and they
may increase libido in humans.
the liver palms, spider angiomas
PROGESTERONE

Secretion Of Progesterone
The follicular phase :
0.9ng/ml ( by the cells in the ovarian
follicle)
The luteum phase :
18ng/ml ( by the corpus luteum)
progesterone
The principal target organs of P are the uterus, the breasts, and the brain.

It has antiestrogenic effects on the myometrial cells


In the breast, progesterone stimulates the development of lobules and alveoli.
The feedback effects of progesterone are complex and are exerted at both the
hypothalamic and the pituitary level. Large doses of progesterone inhibit LH
secretion and potentiate the inhibitory effects of estrogens, preventing
ovulation.
Progesterone is thermogenic and is probably responsible for the rise in basal
body temperature at the time of ovulation.
Progesterone stimulates respiration .
Large doses of progesterone produce natriuresis.
1.the physiological characters of every stage in the
female life
2.the follicular development, maturation, ovulation,
luteinization and luteolysis, and the homones which
the corpus lutum produces, These include :estradiol,
progesterone and androgen
3. the cyclic changes in genital organs induced by
gonadal hormones
4. the regulating mechanism of the menstrual cycle
by the Hypothalamic-Pituitary-ovaries Axis

Gn RH
FSH LH


FSH
LH
LH
LH
LH FSH