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 converted 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+-7 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 initiation & 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.

Physiology of Pregnancy
• Fertilization
• Implantation
• Formation of placenta
• Changes in mother

Maturation of the Ovum
• While still in the ovary, the ovum is in the primary oocyte
stage. Shortly before it is released from the ovarian
follicle, its nucleus divides by meiosis and a first polar
body is expelled from the nucleus of the oocyte. The
primary oocyte then becomes the secondary oocyte.
• In this process, each of the 23 pairs of chromosomes loses
one of its partners, which becomes incorporated in a
polar body that is expelled. This leaves 23 unpaired
chromosomes in the secondary oocyte.
• It is at this time that the ovum, still in the secondary
oocyte stage, is ovulated into the abdominal cavity. Then,
almost immediately, it enters the fimbriated end of one of
the fallopian tubes.

Maturation of the Ovum
• When ovulation occurs, the ovum, along with a
hundred or more attached granulosa cells that
constitute the corona radiata, is expelled directly
into the peritoneal cavity.
• As many as 98 % succeed in entering fallopian tube.
• Women with one ovary removed and the opposite
fallopian tube removed have had several children
with relative ease of conception, thus demonstrating
that ova can even enter the opposite fallopian
tube.

Fertilization of the Ovum
• After the male ejaculates semen into the vagina
during intercourse, a few sperm are transported
within 5 to 10 minutes upward from the vagina and
through the uterus and fallopian tubes to the
ampullae of the fallopian tubes.
• This transport of the sperm is aided by contractions
of the uterus and fallopian tubes stimulated by
prostaglandins in the male seminal fluid and also by
oxytocin released from the posterior pituitary gland
of the female.
• Of the almost half a billion sperm deposited in the
vagina, a few thousand succeed in reaching each
ampulla.

Fertilization
• During sexual intercourse ,millions of sperms
are deposited in vagina.
• Sperms are viable for only 48 hours after
ejaculation.
• They 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.

Fertilization of the Ovum
• Sperm penetration – acrosomal reaction
• Once a sperm has entered the ovum (secondary oocyte),
the oocyte divides again to form the mature ovum plus a
second polar body that is expelled.
• The mature ovum still carries in its nucleus (female
pronucleus) 23 chromosomes.
• On entering the ovum, sperm head swells to form a male
pronucleus. Later, the 23 unpaired chromosomes of the
male pronucleus and the 23 unpaired chromosomes of the
female pronucleus align themselves to re-form a complete
complement of 46 chromosomes (23 pairs).

Implantation of the Blastocyst
• After reaching the uterus, the developing blastocyst
usually remains in the uterine cavity an additional 1 to 3
days before it implants in the endometrium
• Implantation results from the action of trophoblast cells
that develop over the surface of the blastocyst.
• These cells secrete proteolytic enzymes that digest and
liquefy the adjacent cells of the uterine endometrium –
dorsal wall
• Once implantation has taken place, the trophoblast cells
and other adjacent cells proliferate rapidly, forming the
placenta and the various membranes of pregnancy.

Early Nutrition of the Embryo
• Corpus luteum – progesterone - endometrial stromal cells
- extra quantities of glycogen, proteins, lipids and some
minerals
• After implantation, uterine endometrium stromal cells
swell – decidual reaction - the decidua
• As the trophoblast cells invade the decidua, digesting and
absorbing it, the stored nutrients in the decidua are used
by the embryo for growth and development. During the
first week after implantation, this is the only means by
which the embryo can obtain nutrients – 8 weeks
• The placenta also begins to provide nutrition 1 week after
implantation.

Placenta
• While the trophoblastic cords from the blastocyst
are attaching to the uterus, blood capillaries grow
into the cords from the vascular system of the newly
forming embryo.
• Simultaneously, blood sinuses supplied with blood
from the mother develop around the outsides of the
trophoblastic cords. The trophoblast cells send out
more and more projections, which become placental
villi into which fetal capillaries grow.
• Thus, the villi, carrying fetal blood, are surrounded
by sinuses that contain maternal blood.

Placenta
• Final structure - the fetus’s blood flows through two
umbilical arteries, then into the capillaries of the
villi, and finally back through a single umbilical vein
into the fetus.
• The mother’s blood flows from her uterine arteries
into large maternal sinuses that surround the villi
and then back into the uterine veins of the mother.
• Nutrients and other substances pass through the
placental membrane mainly by diffusion in much the
same manner that diffusion occurs through the
alveolar membranes of the lungs and the capillary
membranes.

Placental Permeability
• The major function of the placenta is to provide
for diffusion of foodstuffs and oxygen from the
mother’s blood into the fetus’s blood and
diffusion of excretory products from the fetus
back into the mother.
• Early months of pregnancy – not developed -
thick membrane – less permeability – not grown
- small surface area – less diffusion – later
months vice versa

Diffusion of Oxygen
• The dissolved oxygen in the blood of the large
maternal sinuses passes into the fetal blood by
simple diffusion, driven by an oxygen pressure
gradient from the mother’s blood to the fetus’
blood.
• 50 – 30 = 20 mmHg
• How it is possible for a fetus to obtain sufficient
oxygen when the fetal blood leaving the placenta
has a PO2 of only 30 mm Hg ???

Diffusion of Oxygen
• The curve for fetal hemoglobin is shifted to the left of that
for maternal hemoglobin. This means that at the low PO2
levels in fetal blood, the fetal hemoglobin can carry 20 to
50 per cent more oxygen than maternal hemoglobin can.
• The hemoglobin concentration of fetal blood is about 50
per cent greater than that of the mother – less affinity for
2,3 DPG
• The Bohr effect, hemoglobin can carry more oxygen at a
low PCO2 than it can at a high PCO2.
• The fetal blood entering the placenta carries large
amounts of CO2, but much of this CO2 diffuses from the
fetal blood into the maternal blood.

Double Bohr Effect
• At the same time, because of entrance of fetal carbon
dioxide into maternal blood, partial pressure of carbon
dioxide is very high in mother’s blood. It decreases the
affiity of mother’s hemoglobin for oxygen resulting in
diffusion of more amount of oxygen into the fetal
blood.
•
Double Bohr effect is the operation of Bohr effect in
both fetal blood and maternal blood.

Diffusion of Oxygen / CO2
• Double Bohr effect
• The total diffusing capacity of the entire placenta
for oxygen at term is about 1.2 milliliters of
oxygen/minute/mmHg O2 pressure difference
across the membrane.
• The PCO2 of the fetal blood is 2 to 3 mm Hg
higher than that of the maternal blood. This
small pressure gradient for carbon dioxide across
the membrane is more than sufficient to allow
adequate diffusion of carbon dioxide

Diffusion of Foodstuffs
• Late stages of pregnancy, the fetus often uses as much
glucose as the entire body of the mother uses.
• The glucose is transported by carrier molecule - facilitated
diffusion through the placental membrane.
• High solubility of fatty acids in cell membranes, these also
diffuse from the maternal blood into the fetal blood, but
more slowly than glucose, so that glucose is used more
easily by the fetus for nutrition.
• Ketone bodies and potassium, sodium, and chloride ions
diffuse with relative ease from the maternal blood into the
fetal blood.

Excretion of Waste
• Same as CO2
• NPN such as urea, uric acid and creatinine.
• Urea conc. slightly greater
• Creatinine considerably higher
• diffusion gradients across the placental
membrane

Placenta
• The placenta - major source of estrogens and
progesterone during pregnancy
• - cannot synthesize these hormones by itself -
requires the assistance of both mother and
fetus.

• The fetus, placenta, and mother are
interdependent - functional unit – joint effort
in steroid biosynthesis – lead to the concept of
feto-placento-maternal unit or simply, the
fetoplacental unit

• During pregnancy - maternal levels of
progesterone and estrogens(estradiols,
estrone, estriol) increase - reach
concentrations substantially higher than those
achieved during a normal menstrual cycle.

• HOW ARE THESE ELEVATED LEVELS ACHIEVED?

EARLY IN THE FIRST TRIMESTER
• Early in the first trimester (upto 7 wks after
conception) - hCG that is manufactured by the
syncytiotrophoblast rescues the corpus
luteum – source of estrogen and progesterone
- until fetoplacental unit is able to synthesize
its own estrogen and progesterone.

Corpus luteum of pregnancy
• hCG - also known as second luteotropic
hormone.
• • Actions - similar to LH of anterior pituitary.
• • Maintains functions of corpus luteum upto
7 weeks after conception

ROLE OF hCG
• hCG converts corpus luteum of menstruation
into corpus luteum of pregnancy - stimulates
it to secrete 17 alpha hydroxy progesterone
and lesser amount of progesterone.

AFTER 8 WKS OF GESTATION
• coordinated biosynthetic activity of the
maternal-placental-fetal unit maintains high
levels of progesterone and estrogens.

Placental Progesterone
• Functions
• Helps to preserve the pregnancy by
promoting growth of the endometrium
• Converts secretory endometrium of luteal
phase of menstrual cycle to decidua during
pregnancy
• Marked inhibitory effect on uterine
contractions – by acting on uterine smooth
muscle - maintains quiescence
• Development of alveolar system of breast

• Inhibits uterine prostaglandin production -
promotes uterine quiescence & delays cervical
ripening.
• • Antagonizes the effect of aldosterone –
promotes renal excretion of sodium during
pregnancy
• • Precursor for corticosteroid synthesis by the
fetal adrenal cortex – therefore helps in growth
and development of fetus
• • Inhibits lactation during pregnancy

• Immunosuppressive activity
• Contributes to the immunologically privileged
status of the pregnant uterus – by inhibiting T
lymphocyte mediated processes that play a
role in tissue rejection.

Placental Estrogen
• Functions
• • Enlargement of the uterus, breasts and female
external genitalia.
• • Relaxes various pelvic ligaments and makes the pelvis
more capacious
• • Development of lactiferous ductal system of breast
• • Stimulates prolactin secretion
• • Production of hormone binding globulins in liver
• • Enhance receptor mediated uptake of LDL

Placental Estrogen
• Stimulates cell proliferation of fetal tissue
• Fetal development & organ maturation
• Helps in increasing fetal lung surfactant
production
• Stimulates Leydig cells of male fetus to produce
testosterone ( initial stimulus is by hCG)
• Increases uteroplacental blood flow – ensures
adequate supply of oxygen & nutrients to the
fetus.

Placental Estrogen
• Increase in oestrogen:progesterone ratio –
progression of the stages of labour
• Due to the stimulatory effects of estrogen on:
- Phospholipid synthesis & turnover -
Prostaglandin production - Increases
formation of lysosomes in the uterine
endometrium - Stimulates synthesis of gap
junctions between myometrial smooth muscle
cells

Placental estrogens
• During pregnancy – a woman produces more
estrogen than a normal ovulatory woman
produce in more than 150 yrs.(Tulchinsky &
Hobel 1973)
• 90% of 17β estradiol & estriol secreted by
placenta – enters maternal compartment
• Most of the estrone – enters fetal
compartment

• Conditions – low estrogen production
• Genetic disorders - fetal & placental sulfatase
deficiencies - fetal & placental aromatase
deficiencies
• Absence of fetal signals from the fetal
hypothalamic pituitary adrenal axis – no
stimulus for fetal androgen production
• • Absence of a fetus – molar pregnancy,
pseudocyesis
• • Fetal demise
• • Anencephaly

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.

Placenta
• ENDOCRINE FUNCTION
Hormones secreted by placenta are:
1. Human chorionic gonadotropin
2. Estrogen
3. Progesterone
4. Human chorionic somatomammotropin
5. Relaxin

Human Chorionic Gonadotropin
•
Human chorionic gonadotropin (hCG) is a glycoprotein. Its
chemical structure is similar to that of LH.
• Actions of hCG
i. On corpus luteum: hCG is responsible for the preservation
and the secretory activity of corpus luteum.
• Progesterone and estrogen secreted by corpus luteum are
essential for the maintenance of pregnancy.
• Defiiency or absence of hCG
during the fist 2 months of pregnancy leads to
termination of pregnancy (abortion), because of
involution of corpus luteum.

• ii. On fetal testes: Action of hCG on fetal
testes is similar to that of LH in adults. It
stimulates the interstitial cells of Leydig and
causes secretion of testosterone.
• The testosterone is necessary
for the development of sex organs in male
fetus

• . 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 Chorionic
Somatomammotropin
•
Human chorionic somatomammotropin (HCS) is a
protein hormone secreted from placenta.
• It is often called placental lactogen.
• It acts like prolactin and growth hormone secreted
from pituitary.
• So, it is believed to act on mammary glands and to
enhance the growth of fetus by inflencing the
metabolic activities.
• It increases the amount of glucose and lipids in
the maternal blood, which are transferred to fetus.

Human Placental Lactogen
• Actions of HCS
i. On breasts: In experimental animals,
administration of HCS causes enlargement of
mammary glands and induces lactation. That is
why, it is named as mammotropin.
• However, the action of this hormone on the
breasts of pregnant women is not known.

• On protein metabolism: HCS acts like GH on
protein metabolism. It causes anabolism of
proteins and accumulation of proteins in the fetal
tissues. Thus, the growth of fetus is enhanced

• On carbohydrate metabolism: It reduces the
peripheral utilization of glucose in the mother
leading to availability of large quantity of glucose to the growing
fetus.

• On lipid metabolism: It mobilizes fat from the
adipose tissue of the mother. A large amount
of free fatty acid is made available as the
source of energy in the mother’s body.
• It compensates the loss of glucose from the
mother’s blood to fetus

hCS/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.

Applied aspects
• Plasma 17 α hydroxy progesterone level -
excellent indicator of the activity of corpus
luteum of pregnancy. Peak level - 3 to 4 wks after
conception.
• • Decrease in 17 α hydroxy progesterone & the
dip in progesterone levels – 8 to 10 weeks of
gestation – reflect luteal-placental shift
• • Progesterone supplementation required if
corpus luteum function is compromised before 9-
10 weeks of gestation.

Applied aspects
• Progesterone production continues after fetal
death - Fetal adrenals not essential for
progesterone production – lacks 3βHSD

Applied aspects
• Urinary estriol
• Index of function of fetoplacental unit
• Use is limited now because of various factors
that affect estriol levels: - Moment to
moment fluctuations – single time plasma
measurement is not very conclusive. - Body
position (bed rest, ambulation) affects blood
flow to uterus & kidney. - Drugs like
glucocorticoids & penicillin.

ROLE OF HORMONES IN GROWTH
OF MAMMARY GLANDS
•
Various hormones are involved in the
development and growth of breasts at different
stages:
1. Estrogen
2. Progesterone
3. Prolactin
4. Placental hormones
5. Other hormones.

ESTROGEN
•
Growth of Ductile System
Estrogen causes growth and branching of duct
system; so the normal development of duct
system in breasts at puberty depends upon
estrogen.
• Estrogen is also responsible for the
accumulation of fat in breasts.

PROGESTERONE
•
Growth of Glandular Tissue
The development of stroma of the mammary
glands depends upon progesterone activity.
• Progesterone also stimulates the
development of glandular tissues.

PROLACTIN
•
Prolactin is necessary for milk secretion.
• However, it also plays an important role in growth of mammary
glands during pregnancy.
•
Normally, prolactin is inhibited by prolactin-inhibiting
hormone secreted from hypothalamus.
• However, prolactin secretion starts increasing from 5th month of
pregnancy.
•
At that time, it acts directly on the mammary glands and
causes proliferation of epithelial cells of alveoli.

• Growth hormone, thyroxine and cortisol
enhance the overall growth and development
of mammary glands in all stages.
• Relaxin also facilitates the development
of mammary glands. It is secreted by corpus
luteum, mammary glands and placenta

LACTATION
•
Lactation means synthesis, secretion and
ejection of milk.
Lactation involves two processes:
A. Milk secretion
B. Milk ejection.

MILK SECRETION
•
Synthesis of milk by alveolar epithelium and its passage
through the duct system is called milk secretion.
Milk secretion occurs in two phases:
•
1. Initiation of milk secretion or lactogenesis
2. Maintenance of milk secretion or galactopoiesis.

Initiation of Milk Secretion or
Lactogenesis
•
Although small amount of milk secretion occurs at later
months of pregnancy, a free flow of milk occurs only after
the delivery of the child.
• The milk, which is secreted initially before parturition is
called colostrum.
•
Colostrum is lemon yellow in color and it is rich in
protein (particularly globulins) and salts. But its sugar
content is low. It contains almost all the components of
milk except fat

Role of hormones in lactogenesis
•
Prolactin is responsible for lactogenesis.
• During pregnancy, particularly in later months, large
quantity of prolactin is secreted. But the activity of this
hormone is suppressed by estrogen and progesterone
secreted by placenta.
•
Because of this, lactation is prevented during pregnancy.
Immediately after the delivery of the baby and
expulsion of placenta, there is sudden loss of estrogen
and progesterone. Now, the prolactin is free to exert its
action on breasts and to promote lactogenesis

Maintenance of Milk Secretion or
Galactopoiesis
•
Galactopoiesis depends upon the hormones
like growth hormone, thyroxine and cortisol,
which are essential for continuous supply of
glucose, amino acids, fatty acids, calcium and
other substances necessary for the milk
production

EFFECT OF LACTATION ON
MENSTRUAL CYCLE
•
Woman who nurses her child regularly does not have menstrual
cycle for about 24 to 30 weeks after delivery.
• It is because, regular nursing the baby stimulates
prolactin secretion continuously.
• Prolactin inhibits GnRH secretion resulting in suppression of
gonadotropin secretion.
• In the absence of gonadotropin, the ovaries
become inactive and ovulation does not occur

EFFECT OF LACTATION ON
MENSTRUAL CYCLE
• When the frequency of nursing the baby
decreases (after about 24 weeks) the
secretion of GnRH and gonadotropins starts
slowly.
• When suffiient quantity of gonadotropins is
secreted, the menstrual cycle starts.

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

IMMUNOLOGICAL TESTS
•
Presence of hCG is also determined by using
immunological techniques. Immunological tests
are based on double antigen-antibody reactions.
Commonly performed immunological test is known as
Gravindex test.
„PRINCIPLE
Principle is to determine the agglutination of sheep
RBCs coated with hCG. Latex particles could also be
used instead of sheep RBCs.

Pregnancy Test
• Recently available immunological tests are more
sensitive and involve single step method. Test kit
is available in the form of cards. These pregnancy
test cards can be used even in the fist few days
of conception. Most sensitive test can detect hCG
level as low as 20 mIU/mL

Female reproductive system Physiology

Female reproductive system Physiology

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