Female reproductive system Physiology

Female Reproductive System
Dr Raghuveer Choudhary
Professor
Department of Physiology
Dr S.N.Medical College,Jodhpur

Female Reproductive Organs
• The Female Reproductive organs comprise:
• The Gonads- in the form of two ovaries
• The accessory sex organs consisting of
• The Fallopian Tube
• Uterus
• Cervix
• Upper end of Vagina

THE UTERUS
The uterus is a pear-shaped muscular organ within the
pelvis, located between the bladder and rectum.
The function of the uterus is to support the growing fetus
during pregnancy.
There is dramatic growth of the uterus during pregnancy,
occurring by a process of both muscle cell hyperplasia and
production of new muscle cells from the resident stem cells.
During parturition (childbirth), the uterine smooth muscle
contracts powerfully to expel the fetus.
The uterus is supported in position by several connective
tissue ligaments. Damage to the uterine ligaments (e.g.,
during childbirth) may result in prolapse of the uterus
downward into the vagina.

• The External Genitalia consiting of
• Lower part of vagina
• Clitoris
• Labia majora & minora.

• Female gonads are pair of ovaries in the
abdominal cavity.
• The Gamete(Ovum) dicharged from an Ovary
is generally captured by a funnel shaped
structure, the fimbriated end of the Fallopian
tube.
• The ovum is transported in the fallopian tube
towards the uterus.

10
Uterine Tubes
(Fallopian Tubes)
• Function: events occurring in the uterine
tube
–Fimbriae sweep oocyte into tube, cilia &
peristalsis move it along, sperm reaches
oocyte in ampulla, fertilization occurs
within 24 hours after ovulation & zygote
reaches uterus about 7 days after
ovulation

12
Fallopian Tube Histology
Cilia sweep egg/zygote toward
the uterus

• The Uterus is child bearing organ.
• The Uterus opens in to vagina ,which in turn
opens towards exterior.

Ovary
• The Ovary is covered by a single layer of
flattened cuboidal epithelium.
• In the stroma of the Ovary large number of
immature ova (primary oocytes) are present.
• Each Primary Oocyte is surrounded by several
stromal cells called Granulosa Cells.
• The Primary Oocyte together with the
Granulosa Cells forms a primordial follicle.

Microscopic appearance of the ovary. (Note: the structures shown are not all present at
the same time). In the first half of the menstrual cycle, several oocytes begin to develop as
a cohort of follicles. A single dominant follicle is visible about midcycle and has
differentiated into a large graafi an follicle. Ovulation occurs by forceful rupture of the
graafian follicle. After ovulation, the graafian follicle transforms into the corpus luteum.

Ovary
• At birth each Ovary of a girl has about one
million primordial follicles.
• Most of these fails to mature & are lost
through atresia.
• A women produces only one ovum every
month during her reproductive period ( @15-
50 years of age) which comes arround 400 ova
in a life time.

Ovary
• No ovum is produced during pregnancy
because monthly ovarian cycle is suspended
during pregnancy.
• The monthly cycle is commonly called the
menstrual cycle because it is accompanied by
bleeding from uterus for about 4 days in a
month.

The Menstrual Cycle
• The female reproductive organs undergo
characteristic cyclic changes apprantly in
preparation for fertilization and conception
• In primates there is shedding of uterine
epithelium at a regular interval along with
bledding. This is termed menstruation & cycle
of related events occuring regularly is called
Menstrual Cycle.

The Menstrual Cycle
• The menstrual cycle is due to the cyclical
secretion of pituitary gonadotropins (FSH,LH)
which in tern impart cyclicity to estrogen &
progestron secretion from the ovary.
• The cycle is accompanied by ovarian as well as
uterine changes.
• The cycle begins with puberty (at about 10
years) but first mentruation (menarche)is
generally a few years later (age 12-14 years)

The Menstrual Cycle
• The average duration of the cycle is 28 days
but the normal range is quite wide (20-45
days)
• The days are numbered in terms of menstrual
bleeding ,day 1 of the cycle being the first day
of menstrual bleeding. Ovulation takes place
at about day 14 of the cycle.

The Menstrual Cycle
• If the cycle length is shorter or shorter than 28
days ,the variation is generally in the period
before ovulation.
• That is the interval between ovulation and
end of the cycle is essentially constant at 14
days irrespective of cycle length

The Menstrual Cycle
• Biological rationale of the cycle is apparently
based on the assumption that ovulation may
be soon followed by fertilization.
• The cycle ensures that fertilized ovum will be
received by a well prepared uterus.If however
fertilization does not take place, preparation
of uterus is undone.
• In the process uterine wall breaks down &
bleeds,resulting in menstruation.

Oogenesis
• The ova are all formed in the fetal life and
they lie inside the primordial follicles.
• During fetal life as many as 7 millions
primordial follicles are formed in the ovary.
• Many of them degenerate at birth,number
drop down to 2 million .
• However only half of them are viable.

Oogenesis
• The ova in the primordial follicle undergoes
the first phase of I Meiotic division & get
arrested in the stage of prophase.
• Oocyte maturation inhibitor secreted from
granulosa cell is presumed to be responsible
for the arrest in prophase.
• This stage of arrest continue till the period just
before the ovulation when the first meiotic
division is completed with production of
secondary oocyte & first polar body.

Oogenesis
• The first polar body degenerate and
disappears. The secondary oocyte
immediately enters in to the second meiotic
division.This is arrested at metaphase stage
untill the sperm fertilized the ovum.
• At the time of fertilization ,the second polar
body is given off & the fertilized ovum is now
ready to multiply in to the new offspring.

• As already mentioned at birth only 2 million
primary oocyte survive.
• At puberty the number falls further to only
300000.
• Only about 450 of these attain the mature
stage in female reproductive life.
• At menopause most of ovarian follicles are
exhausted.

• We have seen that development of primary
oocyte is arrested at the prophase stage of
meiosis.
• This prophase stage of meiosis in a primary
oocyte may persist for a period varying
between 15-50 years as ovulation may occur
soon after menarche to just before
menopause.

Ovarian Cycle
• Follicular phase 14+-7 days
• Luteal phase 14 days
• The first half i.e @14 days of the cycle are
occupied by development of follicles.That is
why this phase is called as follicular phase.

Ovarian Cycle(Follicular Phase)
• During the first week of follicular phase a few
primordial follicles start developing.
• But by the end of one week only one follicle
continue to develop further while the
remaining follicles become smaller and
disappear i.e undergo atresia.

42
Zona pellucida
1° Oocyte
(arrested in prophase I)
Granulosa cellsThecal cells
Nucleus
Primordial
follicle
Primary Follicle

43
Secondary Follicle Fluid-filled antrum

44
Graafian Follicle
Fluid filled antrum
Granulosa cells
Oocyte 2°
Corona radiata
Stalk
Zona pellucida

• The follicle that continue to develop finally has
a cavity filled with follicular fluid & on one
side is the ovum surrounded by granulosa
cells.
• The granulosa cells are further surrounded by
two layers of the theca cells : theca interna
&theca externa.
• On the day 14 of the cycle the follicle ruptures
,the ovum together with a few surrounding
granulosa cells is shed in to the abdominal
cavity.

• And the remaining follicle forms the corpus
hemorrhagicum in the ovary.
• The process of ovum being discharged from
follicle is called Ovulation.

• The early growth of follicle is due to the action
of FSH secreted by the anterior pituitory.
• The production of this hormone in chilhood is
negligible but it increases just before puberty.
• It act on the primordial follicle of the ovary &
leads to proliferation and growth of granulosa
cells & theca interna.
• Under the influence of this hormone during
each menstrual cycle one of the primordial
follicle is converted in to graffian follicle.

• Graafian follicle takes 14+- 7 days to mature.
• The granulosa cells & theca interna produce
oestradiol (one of oestrogens)
• This hormone acts on to the genital tract &
cause hypertrophy &hyperplasia of tissues.
• It is responsible for development of secondary
sexual characters.

• Estrogen increses no of FSH receptors on
granulosa cells which in tern leads to release
of more estrogen,resulting in positive
feedback loop.
• Further combined action of FSH &Estrogen
leads to the expression of LH receptors on
granulosa cells &theca cells.
• Availability of LH receptors leads to
progestrone secretion towards the end of
follicular phase.

LH Surge for Ovulation
• Further a finely programmed positive
feedback mechanism leads to a sharp rise in
LH secretion about 6 hours before ovulation.
• The LH surge is essential for ovulation

• LH is produced by the basophil cells of
anterior pituitory.
• It act on mature graafian follicle & leads to
shedding of the ovum & conversion of
graafian follicle in to corpus luteum.
• This hormone is produced in small quantities
continuously but a sudden surge takes place in
the middle of the cycle ,which leads to
ovulation.
• This is due to positive feed back by oestrogens
acting on hypothalamus & anterior pituiory.

Ovarian Cycle(Luteal Phase)
• Sudden surge of Luteinizing Hormone of
anterior pituitory takes place in the middle of
the cycle.
• This hormone acts on the mature graafian
follicles on 13 to 15th day of the ovarian cycle
& cause rupture of the follicle and shedding of
the ovum (ovulation).
• Empty graafian follicle is coverted in to corpus
luteum

• The Corpus Luteum takes 3-4 days to mature
(17-18 days of cycle) & function for 5-6 days
(23rd-24th day).
• It starts degenerating after the 24th day &
degeneration is complete in 4-5 days,by the
end of cycle
• After degeneration corpus luteum finally
acquires a white colour because of fibrin
deposition this is called corpus albicans

• If fertilization of ovum takes place the stage of
degeneration is delayed & Corpus Luteum
continues to function for 13-14 weeks of
pregnancy.
• This is due to production of human chorionic
gonadotropins by the throphoblast of the
fertilized ovum.
• At this stage the placenta takes over the
function from copus luteum completely.

Uterine Cycle
• As seen above ,towards the end of menstrual
cycle the corpus luteum degenerate to form
corpus albicans.
• The degenerated corpus luteum cannot
synthesize much estrogen and progestron.
• Withdrawal of these hormones leads to
breakdown of the uterine wall
&bleeding,resulting in menstruation .
• Conventionally the onset of bleeding is
considererd beginning of menstrual cycle.

Uterine Cycle
• Bleeding continues for about 4 days.
• By day 5 ,the ovarian follicle is sufficiently
developed to secrete considerable quantity of
estrogen,
• The uterine wall not only start getting
repaired but the endometrium thickness also
starts increasing.
• During menstrual cycle all superficial uterine
epithelium is shed

Uterine Cycle
• Endometrium respond to the ovarian
hormones ,estrogen & progestron. The
ovarian activity is divided in to follicular &
luteal phase.
• Estrogens are produed during follicular&
luteal phases but progestron is produced only
by corpus luteum during luteal phase.
• The endometrium respose is accordingly to
the ovarian activity,correspondingly to
follicular &luteal phases

Uterine Cycle
• Acoordingly endometrium response is divided
in to 2 phases
• Proliferative Phase
• Secretory Phase
• The Endometrial cycle correspond to the
ovarian cycle & it lasts for 28+- 7 days

Uterine Cycle(Proliferative Phase)
• This phase starts on first day of menstruation
& last for about (14+- days)
• The following endometrial changes takes
place under the influence of estrogen from
ovaries.
• Menstruation=it last for 2-8 days. The
endometrium is shed during this stage.
• The entire endometrium is not shed
simultaneously, only small area undergoes
necrosis & are lost

• The shedding of endometrium is due to necrosis
of superficial and intermediate zone of
endometrium.
• Withdrawal of hormones causes spasm of blood
vessel which leads to ischaemic necrosis of the
endometrium.
• The blood loss during menstruation is 5-80 ml

• Menstrual contents= blood mixed with shed
endometrium,prostaglandins &fibrinolysin.
• Blood of arterial origin
• Menstrual blood doesnot clot.
• Duration 3-5 days with range 1-8days
• Amount 80 ml

• Reparative stage= after menstruation,most of
the endometrium is lost &only basal layer and
basal part of the glands survive.
• The repair of the endometrium starts during
the menstruation by proliferation of basal
layer of the endometrium and epithelial lining
of the glands.
• The cells of the basal layer proliferate under
the influence of estrogen.

• Following changes takes place during this
stage: The cuboidal epithelial cells of basal
layer proliferate and multiply.
• The endometrium which had become very
thin (1-2mm) due to shedding during
menstruation increases in thickness.
• Blood vessels also multiply in new
endometrium & supply blood.

• The lining cells of endometrial glands undergo
mitosis to form long tubular glands & surface
epithelium of the endometrium.
• The lining of glands changes from cuboidal to
columnar epithelium with a basal nucleus.
• There is no secretory activity in glands during
this phase.
• At the end of this phase of proliferation the
endometrium is vascular & thick(3-4mm)
&tubular glands are straight.

• Cervical epithelium does not undergo cyclical
changes like endometrium.
• In proliferative phase cervical mucous become
thinner & alkaline.
• This facilitate entry of sperms in to the uterine
cavity.

Uterine Cycle(Secretory Phase)
• This phase constitute last 14days of menstrual
cycle &its duration is remarkably constant.
• During this phase endometrium become thick &
hypertropied.
• Glands undergo changes in shape.They become
elongated & coiled. Also they secrete a
thick,viscous glycogen rich fluid.
• In this phase ,stromal cells cytoplasm is increased
in volume ,glycogen and lipid accumulates inside
stromal cells & these can provide nourishment to
ovum after fertilisation until it establises
alternative nutritive source

• Coiled spiral arteries supply stratum
functionale,the superficial 2/3 of
endometrium where as short & straight
basilar arteries supply stratum basale,the
deeper 1/3 of the endometrium.
• These changes were brought by combined
action of estrogen &progestron secreted from
the corpus luteum,prepare the uterus for
implantation of fertilised ovum so this is
known as luteal phase.

• In this phase cervical secretions become thick
preventing entry of sperms.
• At the same time the uterine muscle is
inhibited by progestrone and this minimises
any chance of abortion.

Hormonal Control of Menstrual Cycle
• Main aim of Gn (FSH & LH) is to prepare the
endometrium each month for a pregnancy.
How ?
• Hypothalamus GnRH synthesis &
release of FSH& LH from anterior pituitary.
• Hypothalamic control of ant. Pituitary is
cyclical.

• FSH
• development of ovarian follicles.
• oestrogen secretion from theca interna
cells proliferative changes in endometrium.
• FSH oestrogen to reach a peak at 12-13
days called oestrogen surge
responsiveness of pituitary to GnRH which
within 24 hours a burst of LH secretion(LH
Surge)

• Ovulation occurs about 6-9 hours after LH Surge;
LH is called ovulating Hormone.
• At the same time when LH peak occurs,FSH also
suddenly to peak (FSH Surge)
• After ovulation serum LH & FSH concentration
falls to very low values for rest of the cycle,but as
the corpus luteum is formed serum progestron
concentration s markedly & serum oestrogen &
inhibin B also s (-) FSH & LH secretion via
negative feedback effect on hypothalamus.

• Progestron acts on endometrium primed by
oestrogen secretory phase of
endometrium development.
• If pregnancy occurs:
• Corpus luteum persists & continue to secrete
Estrogen & Progestron however its function
begins to after 8 weeks of pregnancy.if it
fails to secrete P&E spontaneous abortion.

• If no fertilization takes place, corpus luteum
regress sharp fall in P &E
witdrawal bleeding.
• Once luteolysis of corpus luteum begins
Progestron & Estrogen & secretion of FSH &
LH New cycle begins

Oestrogen
• The Physiological active natural oestrogens are
• 17 B oestradiol (most potent)
• Oestrone
• Oestriol (least potent)

Oestrogen
• Sorces-
• Theca interna cells of Graafian follicle (majour
source) These cells have many LH receptors.
• Granulosa cells of Graafian follicle (oestrogen
from this source remains in the follicular fluid)
• Placenta
• Adrenal Cortex (small amount)
• Testis

Oestrogen
• Transport: 97 % circulate in the blood bound
plasma proteins.Albumin (60%) & CBG (37%)
• 3% circulate in blood in free form.
• Daily seceretion : in females 35-500 ug/day (in
different steps of menstrual cycle)
• Two peaks of secretion : 1st just before
ovulation(200-500ug/day); 2nd during mid
luteal phase(250ug/day)
• 15-45mg during pregnancy; to low levels after
menopause.In males 50ug/day

Oestrogen
• Metabolism: conjugated in liver to form water
soluble sulphates & glucoronides which are
then excreted in urine (mainly) & faeces.
• Mechanism of action: being a steroid
hormone act via DNA & RNA : initiate changes
which cell replication /protein synthesis.

Functions of Oestrogen
• Promotes the growth & activity of
ovaries,uterus,vagina.
• Ovaries: responsible for completion of ovarian
cycle.
• Uterus: s mitotic activity in myo &
endometrium growth & blood supply.
• Cervical mucous secretion become copious &
watery.
• Fallopian Tube: secretory activity & motility.

• Growth of external genitalia.
• Responsible for appearance of secondary
sexual characters.
• Influence the gonadotropin secretion.
• Oestrogen in small doses acts directly upon
hypothalamus & anterior pituitary FSH &
LH secretion.
• In large doses positive feedback effect on
LH secretion(by increasing responsiveness of
the pituitary to GnRH)

• Moderate & constant level of Estrogen
produces negative feedback on LH secretion.
• Whereas an elevated Estrogen level produces
positive feedback effect & stimulate LH
secretion.

• Helps for intiation & maintenance of
pregnancy & parturition.
• plasma T4,Cotisol binding globulin &
angiotensinogen.
• serum cholestrol prevent development of
atherosclerosis.

Use Of Oestrogen
• Artificial oestrogens are used clinically :
• to control post menopausal symptoms,
• In the oral contraceptive pills.

Progestron
• Sorces:
• Corpus Luteum & Placenta
• Testis & Adrenal Cortex (in small amount)
• Plama Level: in men =0.3ng/ml
• In women=0.09ng/ml during follicular phase
of menstrual cycle & which by 20 folds
during luteal phase.
• Meatabolism: converted in the liver to
pregnediol which is conjugated to glucuronic
acid & exreted in urine

Progestron
• Mechanism of Action: by action on DNA to
initiate synthesis of new mRNA.
• Actions
• On the estrogen stimulated proliferated
endometrium,it produces secretory changes
which prepare the endometrium for
implantation of fertlized ovum.
• Cervical mucous become thick and tenacious.
• growth of lobules & alveolar tissues in the
breast.

Progestron
• Antagonizes the action of oestrogen e.g.
• excitability of myometrial cells
• sensitivity of myometrium to oxytocine
• number of estrogen receptors in the
endometrium.
• basal body temperature slightly.
• Inhibits ovulation by inhibiting release of
GnRH from the hypothalamus LH
potentiate inhibitory effect of estrogen on
secretion of GnRh

Use of Progestron
• Synthetic progestron preparations in
contraception pills.
• It is of value in pregnant women who have
had repeated abortion by promoting placental
hormone formation or by reducing uterine
contractions

Relaxin
• Sorces: corpus luteum (mainly)
• Uterus & Placenta
• In males prostate gland
• Use: facilitate delivery by relaxation of pubic
symphysis & other pelvic joints;
• Inhibition of uterine contractility.
• Softening & dilatation of cervix.
• In males,helps to maitain sperm motility &
aids in sperm penetration of the ovum.

Removal of Ovary
• Before Puberty
• Puberty doennot set in.
• The Menstrual flow doesnot appear.
• Secondary sexual characters do not develop.

Removal of Ovary
• In Adults: atrophy of the whole genital tract.
• Menstruation ceases permanently.
• Vasomotor changes are common like
• Flushing of skin of face,neck & upper chest called
Hot fluses i.e. sensation of wamth;
• Feeling of suffocation & night sweats
• Effect on breast Variable
• They may increse in size due to local
accumulation of fat or
• They may shrink due to atrophy of glandular
tissues.

Removal of Ovary
• Obesity develops due to diffuse deposition of
fat.
• Effect on sexual desire: variable but
unaffected.
• Emotional disturbance of varying degree of
irritability or depression to insanity.

Fertilization
• During sexual intercourse ,millions of sperms
are deposited in vagina.
• Sperms are viable for only 48 hours after
ejaculation.
• Thet ascends Uterine cavity isthmus of
fallopian tube,
• There they slow down & capacitation occurs

Fertilization
• 3 factors predispose to capacitation in female
genital tract.
• Sperms lose cholestrol in the female genital
tract .This weakens the acrosomal cap.
• The fluid in the female reproductive tract
remove various inhibitory factors attached to
the sperm.
• Ca++ entry in to the sperm enhances flegellar
movement & also helps in release of enzymes
in acrosome.

Fertilization
• Only 50-100 sperms out of the millions
,ultimately reach the ovum.
• The Ovum is liable for fertilisation for a short
period @15-20 hours following ovulation.
• Fertilization normally takes place in ampulla of
the fallopian tube.
• Ovum is surrounded by several layers of
granulosa cells. Penetration of these layers
require a membrane hyluronidase Called PH-
20

Fertilization
• Sperm on reaching the Zona Pellucida after
penitration bind to a protein called ZP-3 on
Zona Pellucida. This induces the acrosome
reaction with disintegration of the acrosomal
cap & release of enzyme like acrosin.
• Sperm then binds to a second protein ZP-2 on
Zona Pellucida . This is followed by
penetration of sperm through Zona Pellucida.

Human Chorionic Gonadotropin
• . hCG is the most important peptide hormone produced by the
placenta because it rescues the corpus luteum from
degeneration and allows continued progesterone secretion to
support the early pregnancy.
• At about 8–9 weeks’ gestation, the placenta will assume the
• production of progesterone.
• Thereafter, the plasma hCG concentrations decrease to lower
levels but continue to be important for maintaining
progesterone secretion by the syncytiotrophoblast.
• Placental hCG secretion is controlled in a paracrine manner by
locally produced GnRH.

Human Placental Lactogen
• Levels of hCS (also called human placental lactogen) are high
during pregnancy. hCS is structurally similar to GH and prolactin.
• Its metabolic effects are similar to those of GH, with suppression
of maternal glucose use and reduced maternal insulin
responsiveness, which may preserve glucose for fetal use.
• Fatty acids and ketones are important energy sources in the fetus
and placenta, and hCS stimulates production of these substrates.
Higher concentrations of hCS found later in pregnancy also promote
mammary gland development.

Fetoplacental Unit
• The fetus ,mother & placenta act in close
cooperation for steroid hormone biosynthesis
in the fetus and placenta,behaving almost as a
functional unit.
• That is why these 3 components acting
together are called the feto-placental-
maternal unit or in short ,the fetoplacental
unit.

Fetoplacental Unit
• The fetal adrenal gland lacks the 3β
dehydrogenase 4,5 isomerase enzyme and so
it is unable to convert pregnenolone to
progesterone.
• As a result ,it depends on progestrone
supplied by the placenta to form aldosterone
and cortisol

• It however,converts pregnenolone in to DHEA-
S (dehydroepiandrosterone sulphate) and
• 16-OH DHEA-S which are formed in fetal liver.
• The placenta,on the other hand lacks, 17
hydroxylase and 17-20 desmolase enzyme.
• So it can not form androgens like DHEA from
progesterone,It therefore depends on the
fetus and the mother for supply of androgens
like DHEA-S which it desulphates & converts to
oestrogens.
Fetoplacental Unit

• However,16-OH DHEA-S is exclusively derived
from the fetus and it is converted in to
oestriol.
• 90% of the urinary oestrogen in mother during
pregnancy is in the form of oestriol derived
entirely from the fetoplacental unit.
• So measurement of urinary oestriol provides a
good index of fetal well-being.
Fetoplacental Unit

Steroid production by the maternal-placental-fetal unit. DHEA, dehydroepinandrosterone;
DHEA-S, dehydroepiandrosterone sulfate; 16-OH-DHEA-S,
16-hydroxy dehydroepiandrosterone sulfate; LDL, low-density lipoprotein.

Failure to Reject the “Fetal Graft
• It should be noted that the fetus and the
mother are two genetically distinct
individuals, and the fetus is in effect a
transplant of foreign tissue in the mother.
• However, the transplant is tolerated, and the
rejection reaction that is characteristically
produced when other foreign tissues are
transplanted fails to occur. The way the “fetal
graft is protected is unknown

Failure to Reject the “Fetal Graft
• However, one explanation may be that the
placental trophoblast, which separates maternal
and fetal tissues, does not express the
polymorphic class I and class II MHC genes and
instead expresses HLA-G, a nonpolymorphic
gene.
Threfore, antibodies against the fetal proteins do
not develop.In addition, there is Fas ligand on the
surface of the placenta, and this binds to T cells,
causing them to undergo apoptosis

Female reproductive system Physiology

Female reproductive system Physiology

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