1. PLACENTAL HORMONE
MJ RASAEE
TMU TEHRAN UPDATED SEP 2020
1

2. placenta’ originates from the Latin word for ‘flat cake’. referred to as the ‘afterbirth’ placenta and the attached
membranes emerge after the baby has been born, and the midwife or doctor will then examine the placenta to
assess its general condition and see whether there are any abnormalities or bits remaining inside mum. The
placenta is disposed of and some times used for protein production , but how this is done differs from culture to
culture and family to family. In some countries, it is not unusual for the placenta to be treated like clinical waste
and quickly bagged and binned. Melsmon Pharmaceutical Co. is a registered pharmaceutical company in Japan, in
operation since 1956, that produces pharmaceutical grade placenta extracts from human placenta. The indication
is to treat menopause. Laennec, another placenta extract formulation, is prescribed to treat chronic hepatitis.
Plantec Co. in Japan makes a drink called "Placenta Drink" which contains placenta. The company claims that "It
is a drink that used the placenta raw material" [sic] and "The expectation that makes the body metabolism active
can be done" [sic] and "It is a drink of the apple taste" [sic]
2
1 Stem Cell Research
2 Chronic Fatigue
3 Wound Healing
4 Anti-Aging Skin Cream
5 Injections
6 Skin Lightening Soap
7 Pills
8 Eye Surgery
9 Luxury Shampoo
10 Face Masks

3. 3
Members of the animal kingdom have
developed a wide range of strategies to pass
on their genes to future generations. An
important part of this is to protect any
offspring from the time of conception to a
point where they can take care of themselves.
Ways of protecting the embryo include
surrounding it by a hard membrane or shell or
by allowing the embryo to develop within the
parental organism. Many species have taken
this second route to embryo protection
including representatives of all the vertebrate
taxa except for the birds, however, it is only
the eutherian mammals that have evolved a
complex organ (the placenta) that is a mixture
of maternal and fetal material and has three
main roles.
1. It was in 480 BC as being the first to suggest that the placenta
was involved in fetal nutrition.
2. Aristotle (384-322 BC) took this idea further, realizing that the
fetus is fully enclosed in membranes, he also believed that the
umbilical chord transferred nutrients from the mother to the fetus
by direct communication of the maternal artery to the fetal artery.
3. William Harvey (1578-1657) suggested that the maternal and fetal
blood systems must be separate
4. 1668 John Mayow postulated that the maternal blood supplies the
fetus with nitro-arterial spirits (oxygen).
5. Halbin, 1905 postulated that the placenta had an endocrine role.
6. the most comprehensive definition is "an apposition of parental
(usually maternal) and fetal tissue for the purposes of physiological
exchange" (Mossman, 1937).
7. However suggestion of "an arrangement of one or more
transporting epithelia between fetal and maternal circulations"
(Steven, 1975) better portrays the functional aspects of the role of
the placenta.

4. 4
functions :To produce a range of steroid and protein hormones that are thought to play a role in the maintenance of
pregnancy as well as in fetal development. Involved in the blocking of further ovarian follicular development and
ovulation
-The blocking of the uterine contractile response to a foreign body
-Ensuring the continued secretion of nutrients by the maternal endometrial glands;
-The mobilization of metabolic reserves such as fats within the maternal organism
-To cause the development of mammary growth and development
-To provide a barrier between the embryo and mother to stop the immunologic attack by the mother against the foreign
implanting embryo.
-To enable the selective exchange of a wide range of substances between the mother and the fetus, for example the
transport of nutrients and gasses and protecting the fetus from toxic chemicals and bacteria. This exchange of materials
requires a wide range of transport processes including passive diffusion, active transport, pinocytosis
Phagocytosis.
-Control local environment of the fetus
Regulate metabolic activities of mother ,
Regulate metabolic activities of fetal tissue

5. Inner cell mass
Destined to
become fetus
Trophoblast
Accomplishes implantation and develops
into fetal portions of placenta
Blastocyst
(cross section)
Blastocoele Becomes amniotic sac
Morula
Cleavage
Spermatozoa
Ovum
(cross
section)
Fertilization
Secondary oocyte (ovum)
Ovulation
Ovary
Implantation
Endometrium of uterus
5
After conception the morula enters the uterus and
develops into the blastocyst (a central cavity
(blastocoele) surrounded by a cell monolayer the
trophoectoderm), there is no increase in size at this
point just an increase in cell numbers.
The zona pellucida (a glycoprotein coat that surrounds
the oocyte and then the blastocyst) either ruptures as
the blastocyst begins to grow or is lysed by uterine
and/or embryonic proteases . The blastocyst then
normally implants into the mid-line of the upper part
of the posterior wall of the uterus. The first stage
being a change in the structure of the trophoblast cells
with a reduction in the number of apical microvilli
allowing a closer association of the trophoblast cells
and the uterus.

6. 6
• THE PLACENTA DEVELOPS AS A SPECIALIZED REGION OF
THE COMPLETE SAC-LIKE STRUCTURE SURROUNDING
AND ENCLOSING THE BABY - THE CHORION - TOGETHER
WITH ADJACENT ENDOMETRIAL TISSUES. TO
UNDERSTAND THE ORIGIN OF THE CHORINE, THINK
BACK TO THE BLASTOCYST STAGE THAT IS REACHED BY
THE CONCEPTUS SHORTLY BEFORE IMPLANTATION IN
THE UTERUS AT THE END OF THE FIRST WEEK OF
DEVELOPMENT. AT THIS TIME, THE OUTER GROUP OF
EMBRYONIC CELLS FORM A HOLLOW SPHERE KNOWN AS
THE TROPHOBLAST (TROPHO- MEANS NUTRITION, AND -
BLAST MEANS A PRECURSOR OR FORERUNNER), AND
INSIDE IT IS A CLUSTER OF CELLS KNOWN AS THE INNER
CELL MASS.
AS IMPLANTATION PROGRESSES, TWO LAYERS SOON BECOME
IDENTIFIABLE IN THE TROPHOBLAST: AN OUTER
SYNCYTIOTROPHOBLAST, INNER CYTOTROPHOBLAST. THE PREFIX
SYNCYTIO- MEANS THAT THIS LAYER IS A SYNCYTIUM - IT IS NOT
SUBDIVIDED INTO DISCRETE CELLS, BUT CONSISTS OF AN
EXTENSIVE LAYER OF CYTOPLASM CONTAINING MANY NUCLEI.
THEREFORE, SYNCYTIOTROPHOBLAST IS THE OUTER SYNCYTIAL
LAYER DERIVED FROM THE ORIGINAL TROPHOBLAST. YOU WILL BE
AWARE THAT SYNCYTIA ARE UNUSUAL IN THE HUMAN BODY - MOST
TISSUES ARE MADE OF INDIVIDUAL CELLS, EACH WITH A SINGLE
NUCLEUS.

7. PLACENTAL
FORMATION
• THIS IS THEN FOLLOWED BY INTERDIGITATION OF THE UTERINE
MICROVILLI AND THE TROPHOBLASTS CELL MEMBRANE. THE
TROPHOBLASTIC CELLS PENETRATE THE UTERINE EPITHELIUM
INTO THE UNDERLYING STROMA. AS THIS PENETRATION
OCCURS THE TROPHOBLAST DIFFERENTIATES INTO TWO
LAYERS, THE CYTOTROPHOBLAST AND THE
SYNCYTIOTROPHOBLAST WHICH IS A SYNCYTIUM MADE OF
MATERNAL AND TROPHOBLASTIC NUCLEI.
SYNCYTIOTROPHOBLAST CELLS CONTINUE TO PROLIFERATE
THEY DELINEATE EXTRACYTOPLASMIC CAVITIES. THESE
CAVITIES INCREASE IN SIZE AND COMMUNICATE WITH ONE
ANOTHER, PRODUCING A SPONGY STRUCTURE (
SYNCYTIOTROPHOBLAST CELLS).
• THE LYTIC ACTIVITY OF THE SYNCYTIOTROPHOBLAST CELLS
CAUSES THE RUPTURE OF BOTH MATERNAL ARTERIAL AND
VENOUS BLOOD VESSELS WITH A RESULTANT FLOW OF
MATERNAL BLOOD FROM THE ARTERIES INTO THE LACUNAR
SPACES AND BACK INTO THE MATERNAL SYSTEM VIA THE
VEINS. PRIMARY VILLI ARE FORMED BY THE TROPHOBLAST
CELLS (THEY HAVE A CORE OF CYTOTROPHOBLAST CELLS AND
A SYNCYTIOTROPHOBLAST COVERING), THEY ARE THEN
INVADED BY MESENCHYME CELLS THEY ARE TRANSFORMED
INTO SECONDARY VILLI. WITHIN THESE SECONDARY VILLI
VESSELS ARE FORMED WHICH WILL LATER JOIN WITH VESSELS
FORMED IN THE EMBRYO THUS CREATING THE CIRCULATION
7
Decidua
Cords of
trophoblastic
cells
Inner cell mass
Surface of
uterine lining
Implantation
Formation of the placental villi
Development of blood supply

8. 8
• THE PLACENTA CONTINUES TO GROW AND DEVELOP THROUGHOUT PREGNANCY AND AT TERM IS AN ORGAN OF ABOUT
20CM IN DIAMETER, WITH A THICKNESS OF 3CM AND A WEIGHT OF ABOUT 500G. THE CHORIONIC VILLI HAVE AN
ENORMOUS AREA OF EXCHANGE, REACHING 14M2 AT TERM AND THE CAPILLARIES WITHIN THEM HAVE A LENGTH OF
50KM. THE RATE OF MATERNAL BLOOD FLOW TO THE UTERUS IS IN THE RANGE OF 500-700ML/MIN WITH 80% OF THAT
DESTINED TO SUPPLY THE PLACENTA . GROWTH MOSTLY DUE TO GH FROM THROPHOBLAST AND GHBP FROM
ENDOMETRIUM AND OXYGEN TENSION CAUSE CYTOTROPHOBLAST CELL PROLIFERATION

9. 9
vital importance to the growth and
development of the fetus. The transport of a
substance from the mother to the fetus or
visa versa depends on:-
i.The concentration of the substance in the
maternal circulation
ii.The mechanism of transfer across the
placental cell membranes, e.g. diffusion,
active transport or receptor sites
iii.The concentration of the substance in the
lacunae
iv.The availability of appropriate carrier
proteins if they are required
v.The placental consumption of the
substance
vi.The concentration in the blood feeding the
fetal side of the placenta .
Vii.The transport of substances cross the
placenta by a number of different routes
including simple diffusion, active transport,
facilitated ionic diffusion, endocytosis or
leakage.
Exchanges across the placenta

10. 10
HORMONAL SECRETION BY THE PLACENTA
relaxin, cytokines like colony stimulating factor I ,
growth factors like IGF-I ,EGF , FGF and IGF-
binding protein

11. 11
• AT CONCEPTION PROGESTERONE PRODUCTION IN THE CORPUS LUTEUM
IS INCREASED .INHIBITS THE NORMAL OESTRUS CYCLE AND ALLOWS
PREGNANCY TO CONTINUE. CONTINUED BY THE CORPUS LUTEUM FOR
ABOUT 50 DAYS AFTER WHICH CYTOTROPHOBLAST AND
SYNCYTIOTROPHOBLAST OF THE PLACENTA TAKE OVER THE
PRODUCTION OF PROGESTERONE . INCREASE DURING PREGNANCY BUT
THERE IS A MARKED SPECIES VARIATION IN PROGESTERONE LEVELS
AROUND PARTURITION.
• IN SOME SPECIES THERE IS A MARKED DROP IN THE LEVELS OF
PROGESTERONE JUST BEFORE THE BEGINNING OF PARTURITION, E.G. THE
EWE (FEMALE SHIP) .IN THE HUMAN THERE HAVE BEEN A NUMBER OF
DIFFERING OBSERVATIONS SUGGESTING THAT THERE IS A MARKED DROP
IN PROGESTERONE PRIOR TO PARTURITION. OTHER STUDIES HAVE NOT
REPLICATED THIS FINDING. IN SUMMARY, IT SEEMS THAT IN MOST
SPECIES THERE IS EVIDENCE THAT A DROP IN PROGESTERONE LEVELS
PRECEDES PARTURITION WAS NEEDED FOR THE UTERINE CONTRACTIONS.
• IN PRIMATES THERE IS NO CLEAR EVIDENCE THAT A DROP IN
PROGESTERONE LEVELS IS NEEDED FOR PARTURITION TO OCCUR, IT
SHOULD BE NOTED HOWEVER, THAT THE MEASUREMENT OF PLASMA
LEVELS OF HORMONES MAY NOT BE INDICATIVE OF THEIR LEVELS AT THE
SITE OF ACTION.
•
‫جد‬ ‫سیکل‬ ‫جلوی‬ ‫و‬ ‫تولید‬ ‫زرد‬ ‫جسم‬ ‫توسط‬ ‫تخم‬ ‫تشکیل‬ ‫دوران‬ ‫در‬ ‫پروژسترون‬
‫را‬ ‫ید‬
‫میگیرد‬
.
‫از‬ ‫پس‬
50
‫جایگزی‬ ‫تروفوبالستها‬ ‫سینسیو‬ ‫و‬ ‫سیتوتروفوبالستها‬ ‫روز‬
‫و‬ ‫میشوند‬ ‫ن‬
‫میابد‬ ‫افزایش‬
.
‫زما‬ ‫در‬ ‫پروژسترون‬ ‫شدید‬ ‫کاهش‬ ‫گوسفند‬ ‫مثل‬ ‫ها‬ ‫گونه‬ ‫برخی‬ ‫در‬
‫وضع‬ ‫ن‬
‫میدهد‬ ‫رخ‬ ‫حمل‬
.
‫نمیشود‬ ‫دیده‬ ‫پروژسترون‬ ‫کاهش‬ ‫از‬ ‫متقن‬ ‫شواهد‬ ‫جوندگان‬ ‫در‬
.
‫چند‬ ‫هر‬
‫داد‬ ‫قرار‬ ‫توجه‬ ‫مورد‬ ‫صرفا‬ ‫نباید‬ ‫را‬ ‫پالسمایی‬ ‫کاهش‬
In the human placenta progesterone is derived from
maternal cholesterol bound to low-density lipoprotein
(LDL) with many functions.
1. It stimulates the growth of the uterus
2. It causes “maturation” (i.e., differentiation) of the
endometrium, converting it to a secretory type.
3. Preparation of endometrium (desicualization )for
implantation
4. Maintenance of endometrium integrity
5. Promotes the production of cervical mucus plug
6. Suppressing T lymphocyte tissue rejection
7. Reducing myometrial contraction (prevents
premature labor)
8. Decreasing the prostaglandins
9. Inhibition of gap junction
10. GABA inhibitor and stimulator
11. Prepares mammary glands for lactation

12. 12

13. 13
Pregnant women and animals have increased susceptibility to a variety of
intracellular pathogens including Listeria monocytogenes (LM), which has been
associated with significantly increased level of sex hormones such as progesterone.
CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-γ responses are
critically required in the host defense against LM. in pregnant women that
increased serum progesterone levels are associated with DNA hypermethylation of
IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon
antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation
and significantly reduced IFN-γ production post LM infection in antigen-non-specific
CD8 Tm cells are also observed in pregnant mice or progesterone treated non-
pregnant female mice, which is a reversible phenotype following demethylation
treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone
treated mice have impaired anti-LM protection when adoptive transferred in either
pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment
rescues the adoptive protection of such CD8 Tm cells.
Suppressing T lymphocyte tissue rejection
uNK cells are the predominant lymphocyte population in
the late secretory phase of the menstrual cycle and in the
early pregnant uterus representing circa 70% of all
leukocytes in decidual tissue. uNK cells differ from
peripheral NK cells in the expression of their receptor
repertoire and in the expression of some genes induced by
the hormonal environment. The main function of uNK cells
is to regulate maternal uterine vasculature remodeling . it
has been demonstrated in the murine system that uNK
cells produce proangiogenic factors such as VEGF and
growth factors and provide local IFN-γ for initiation of
spiral artery formation
Correlation between
progesterone and IFN-
γ production and IFN-
γ gene methylation in
human CD8 Tm cells

14. ACTION OF
ESTROGENS
14
• ROLE IN IMPLANTATION AND IN MAMMARY GLAND DEVELOPMENT IN
THE RELEASE OF PROLACTIN AT PARTURITION. IN THE EWE THE AMOUNT
OF ESTOGENS IN THE MOTHERS PLASMA RISE SLOWLY UNTIL DAY 145-
150 OF PREGNANCY WHEN THERE IS A SHARP INCREASE IN THE LEVEL.
• MATCHES THE FALL IN THE LEVEL OF PROGESTERONE IN THE EWE .IN
HUMANS, THE LEVELS OF ESTROGENS IN MATERNAL PLASMA APPEAR TO
RISE THROUGHOUT PREGNANCY, BUT AS WITH PROGESTERONE THERE IS
A DIFFERENCE OF OPINION AS TO WHAT HAPPENS PRIOR TO
PARTURITION.
• GROWTH OF THE MYOMETRIUM AND ANTAGONIZE THE MYOMETRIAL-
SUPPRESSING ACTIVITY OF PROGESTERONE. IN MANY SPECIES, THE HIGH
LEVELS OF ESTROGEN IN LATE GESTATION INDUCES MYOMETRIAL
OXYTOCIN RECEPTORS, THEREBY PREPARING THE UTERUS FOR
PARTURITION. INCREASE MYOMETRIAL GAP JUNCTION
• STIMULATE MAMMARY GLAND DEVELOPMENT. ESTROGENS ARE ONE IN A
BATTERY OF HORMONES NECESSARY FOR BOTH DUCTAL AND ALVEOLAR
GROWTH IN THE MAMMARY GLAND.
• ALTER THE UTERINE BLOOD FOLLOW

15. ESTROGEN IN
PARTURITION
SHARP RISE IN LEVELS PRIOR TO PARTURITION OTHER
STUDIES HAVE NOT REPLICATED THIS FINDING .IN
SOME SPECIES ESTROGENS ARE PRODUCED ENTIRELY
IN THE PLACENTA BY SYNTHESIS FROM C21 STEROID
PRECURSORS (E.G. PREGNENOLONE AND
PROGESTERONE), HOWEVER, IN MAN, WHO LACKS
THE NECESSARY ENZYMES FOR THIS PATHWAY,
ESTROGENS ARE PRODUCED FROM ANDROGENS
SECRETED BY THE FETAL ADRENAL GLAND. MAN IS
THEREFORE SAID TO POSSES A 'FETOPLACENTAL
UNIT' BECAUSE BOTH THE FETUS AND THE PLACENTA
ARE REQUIRED TO COMPLETE THE STEROIDOGENIC
15

16. ESTROGENS PRODUCTION AND
METABOLISM
16
Fetal adrenal cortex ( 85% of cortex 10 g at birth
,25 times of adult adrenal under fetal pituitary ACTH
and CG CS ,deficient of 3B-OHSD ) .Producing 200
mg of steroids (DHEA and DHEA-S produced from
pregnenolone sulfate of adrenal and pregnenolone by
placenta metabolized by fetus liver to 16 OH DHEA
and further metabolism by placenta ).The key
enzyme aromatase in placenta( producing E2 and E3
,factor determine the rate of synthesis the sizes of
fetal adrenal, stimulation by tropic hormones
,availability of LDL and mass of synsitiotrophoblast)
.E1,E2,E3,E4 (all produced during pregnancy and is
metabolized by mothers liver as sulfo and
glucoronide conjugate and excreted from urine)
50% hepatic
25% 5 alpha reduction sulphated and 25%------ in blood to
5 beta glucoronidated ------ urine
50% extrahepatic
40% 5 alpha reduction ----5 alpha-pregnanediols in
blood
3% 21 OH-------- DOC ----- blood

17. 17
Concentration of estrogen , progesterone
and weight of placenta in human
1: 3 B-OHSD; 2: 17-OHSD; 3: AROMATASE;
4: 16 A-OH LASE; 5: 17 A OH LASE;6:
DECARBOXYLASE.

18. 18
CHORIONIC GONADOTROPHIN
(CG)
IS A MEMBER OF THE GLYCOPROTEIN FAMILY OF PEPTIDE HORMONES THAT INCLUDES LUTEINISING
HORMONE (LH), FOLLICLE-STIMULATING HORMONE (FSH) AND THYROID-STIMULATING HORMONE (TSH).
CHORIONIC GONADOTROPHIN HAS AN EFFECT ON A NUMBER OF ORGANS AND SYSTEMS
regulating the production of progesterone by the corpus luteum in early
pregnancy. injecting human CG (hCG) into corpus luteum cells resulting in an
increase in progesterone secretion by the corpus luteum.
Holo HCG clears in two phase (6 and 36 h).Proteolysis is
taking place between aa 44 or 47 & 48.

19. PLACENTAL LACTOGEN (PL) ALSO KNOWN AS CHORIONIC
SOMATOMAMMOTROPHIN
IS A MEMBER OF THE GROWTH HORMONE AND PROLACTIN FAMILY OF HORMONES.
SHOWS AN 85% HOMOLOGY TO HUMAN GROWTH HORMONE (HGH) A 67%
HOMOLOGY TO PROLACTIN (PRL) .HPL BINDS TO BOTH HGH AND PRL RECEPTORS
MOST OF THE WORK DONE ON THE ROLE OF HPL IN PREGNANCY HAS EXAMINED
PROCESSES THAT ARE REGULATED BY GROWTH HORMONES AND PRLS. IS
PRODUCED IN THE SYNCYTIOTROPHOBLAST FROM THE 5TH WEEK OF
PREGNANCY AND IS SECRETED INTO THE MATERNAL BLOODSTREAM. THE
SECRETARY RATE OF HPL INCREASES GRADUALLY UNTIL TERM AT WHICH TIME
THE PLACENTA MAY BE PRODUCING BETWEEN 0.3 AND 1.0 G/DAY. THIS HORMONE
IS REGULATED BY ESTROGEN. STIMULATION OF FETAL GROWTH: THE POTENCY OF
PL IN PROMOTING GROWTH IS VERY LOW. HPL PLAYS A ROLE IN REGULATING
GROWTH-ASSOCIATED PROCESSES IN SEVERAL FETAL TISSUES. HPL STIMULATES
AMINO ACID UPTAKE, THYMINE INCORPORATION AND INSULIN-LIKE GROWTH
FACTOR-1 (IGF-1) PRODUCTION IN FIBROBLAST AND SKELETAL MUSCLE
MYOBLASTS
HPL IN THE HUMAN MAMMARY GLAND WOULD APPEAR TO BE TO STIMULATE CELL
PROLIFERATION RATHER THAN SECRETION ALTHOUGH HPL STIMULATES
LACTOGENESIS IN NON-PRIMATE SPECIES.
REGULATION OF STEROIDOGENESIS ,
INCREASE IN BASAL LIPOLYSIS ,
INCREASE IN LIPID MOBILIZATION ,
STIMULATING GLUCOSE UPTAKE AND UTILIZATION. THE NET EFFECT OF THESE
CHANGES BEING TO FREE-UP MATERNAL GLUCOSE FOR THE FETUS AND
STIMULATED INSULIN SECRETION, DEVELOPMENT OF INSULIN RESISTANCE BY
SOME TISSUES,IMPAIRED CARBOHYDRATE TOLERANCETHE REGULATION OF
MATERNAL INTERMEDIARY METABOLISM:
PL IS THOUGHT TO PLAY A ROLE IN SOME OF THE LIPID AND CARBOHYDRATE
METABOLISM CHANGES THAT OCCUR IN THE MOTHER DURING THE THIRD
TRIMESTER OF PREGNANCY.
STIMULATION OF FETAL GROWTH: HPL PLAYS A ROLE IN REGULATING GROWTH-
ASSOCIATED PROCESSES IN SEVERAL FETAL TISSUES. HPL STIMULATES AMINO
ACID UPTAKE, THYMINE INCORPORATION AND INSULIN-LIKE GROWTH FACTOR-1
(IGF-1) PRODUCTION IN FIBROBLAST AND SKELETAL MUSCLE MYOBLASTS
19
The presence of antisera against hPL, IGF-I
and -II abolished the hPL-induced increase in
the development in all parameters suggesting
that there may be a possible link between the
IGFs and the effects of hPL on rat embryonic
development and this hormone may achieve
its growth promoting effects via IGFs.HPL
values are decreased with:Toxemia,Aborting
hydatidiform mole,Choriocarcinoma ,Placental
insufficiency ,HPL values are increased
with:Multiple pregnancies (twins or more),
Placental site trophoblastic tumor,Intact molar
pregnancy ,Diabetes,Rh incompatibility

20. 20
• PROLACTIN IS A HORMONE THAT PLAYS A
ROLE IN FERTILITY BY INHIBITING FOLLICLE
STIMULATING HORMONE (FSH) AND
GONADOTROPIN-RELEASING HORMONE
(GNRH), THE HORMONES THAT TRIGGER
OVULATION AND ALLOW EGGS TO DEVELOP
AND MATURE
• PROLACTIN IS SECRETED BY THE DECIDUAL
STROMAL CELLS INTO THE AMNIOTIC FLUID.
IT'S ROLE IS UNCLEAR BUT IT WOULD APPEAR
TO REGULATE THE COMPOSITION AND
VOLUME OF THE AMNIOTIC FLUID
Units Nonpregnant
Female
First
Trimester
Second
Trimester
Third
Trimester
ng/mL 0 - 20 36 - 213 110 - 330 137 - 372
µg/L 0 - 20 36 - 213 110 - 330 137 - 372
pmol/L 0 - 859 1,565 - 9,261 4,783 - 14,347 5,957 - 16,174
Prolactin concentration (serum)
hGH-V which differs in 15 amino acid positions from hGH
has been found in the placenta. Its role similar to pituitary
GH in that it has a somatogenic activity and during the
second half of pregnancy it may regulate many of the
processes normally regulated by pituitary GH in non-
pregnant individuals . hGH-V and insulin-like growth factor-1
(IGF-1) during pregnancy have shown a correlation possible
role for hGH-V in regulating IGF-1 production in the second
half of pregnancy .
produced by the syncytiotrophoblast cells and is found in
the maternal blood from about weeks 21 to 26, increases
until about week 36 and then remains constant for the
remainder of pregnancy . It is possible that hGH-V is in the
maternal blood system from week 9 at low levels since
mRNAs for hGH-V are present in placenta from that time.
Gonadotrophin releasing hormone
(GnRH): It has been found that the
cytotrophoblast of the human placenta
has a GnRH activity. In vitro GnRH
stimulates hCG secretion, this increase
in stimulation is more marked in early
gestation than is found at a later time
point

21. •It has been suggested that hCG has a role in regulating fetal testicular steroidogenesis. concentrations of testosterone in the blood of male fetuses peaks
between 11 and 17 weeks post conception which coincides with or is shortly after the maximum concentrations of hCG in the fetal serum. Outocrine-paracrine
role on the placenta, Effect on the endometrium. Increase fetal testosterone ,Increase fetal DHEA,Binding to TSH receptor (increase maternal thyroxin)
,Maintain corpus luteum . hCG might play a part in regulating steroid production in the fetal adrenal late in the first trimester and early in the second trimester
of pregnancy, but it is not clear whether or not hCG is required for normal development of the fetal adrenal .Again the adenylate cyclase-cAMPpathway might
well mediate the action of hCG in this tissue . CG plays a role in regulating placental growth and the production of other placental hormones and growth
factors. These include oestrogens, progesterone, placental inhibin, IGF-II and prolactin. The mechanism of CG action in the placenta is not well known,
however it may be that the adenylate cyclase-cAMP pathway is involved in mediating CG action .
21
• GNRH,EGF,CSF-1 STIMULATING
CAMP
• CYTOKINE II-1,IL6
• CG ITSELF INCREASING CAMP
• INHIBIN AND ACTIVIN PRODUCED
BY PLACENTA FORMER BLOCKS
GNRH AND LATER STIMULATES IT
• PROGESTERONE INHIBIT CG
PRODUCTION
CONTROL OF CG PRODUCTION
Pregnancy monitor (gestational time ,growth ,ectopic pregnancy, viable and
healthy placenta etc).Triple screening to asses genetic disease(afp,CG and
unconjugated E3).Gestational trophoblastic disease and nor throphoplastic tumor

22. • THE PLACENTA CONTAINS A NUMBER OF FACTORS THAT ARE SIMILAR IN STRUCTURE TO, OR
THE SAME AS,THEIR HYPOTHALAMIC COUNTERPARTS LIKE PLACENTAL CRH
• INCREASE IN TWINE PREGNANCIES
• GLUCOCORTICOIDS STMULATES TROPHOBLASTIC CRH GENE EXPRESSION
• REGULATED BY PLACENTAL NEUROPEPTID Y
• CONTRIBUTES TO INCREASES IN LEVELS OF MATERNAL ACTH DURING PREGNANCY PRODUCED
BY CYTOTROPHOBLAST, THE DECIDUA AND THE AMNION. PLACENTAL CRH, WHICH DOES NOT
FOLLOW A CIRCADIAN RHYTHM,
• CONTRIBUTES TO HYPERCORTISOLISM AND A BLUNTED DIURNAL PATTERN OF CORTISOL
PRODUCTION. UNLIKE HYPOTHALAMIC CRH, WHICH IS UNDER THE CONTROL OF
GLUCOCORTICOID NEGATIVE FEEDBACK, BOTH IN VIVO AND IN VITRO PLACENTAL CRH
PRODUCTION ARE STIMULATED BY FETAL CORTISOL
22
restore local blood flow
CRF has been identified in the placenta and is secreted from the
cytotrophoblast, the decidua and the amnion.It has been found
that CRF in the maternal plasma rises exponentially from about 20-
24 weeks to term and as such it is possible that CRF might play a
central role in the mechanisms leading to term and pre-term
labour. Fetal adrenal steroid production is regulated directly by
both ACTH and CRH. In late gestation, the fetal adrenal glands
initiate cortisol production, which leads to a feed-forward cascade
that increases fetal adrenal production of both cortisol and DHEAS.

23. 23
PLACENTAL-DERIVED CRH CONTRIBUTES TO INCREASES IN LEVELS OF MATERNAL ACTH DURING PREGNANCY. PLACENTAL CRH, WHICH
DOES NOT FOLLOW A CIRCADIAN RHYTHM, CONTRIBUTES TO HYPERCORTISOLISM AND A BLUNTED DIURNAL PATTERN OF CORTISOL
PRODUCTION INTERESTINGLY, UNLIKE HYPOTHALAMIC CRH, WHICH IS UNDER THE CONTROL OF GLUCOCORTICOID NEGATIVE
FEEDBACK, BOTH IN VIVO AND IN VITRO PLACENTAL CRH PRODUCTION ARE STIMULATED BY FETAL CORTISOL. FETAL AND MATERNAL
ADRENAL GLANDS CONTRIBUTE DHEAS FOR PLACENTAL PRODUCTION OF OESTRONE AND OESTRADIOL. PLACENTAL METABOLISM OF FETAL-
DERIVED 16OH-DHEAS AND 15,16OH-DHEAS GIVES RISE TO OESTRIOL AND OESTETROL.

24. ß-endorphin is secreted by the placental cytotrophoblast,
decidua and amnion. It's role is unclear but because of the
analgesic properties of endorphins it is possible that
changes in the amounts in the peripheral blood system of
the mother may underlie changes in pain perception during
labor, or, that changes in endorphin secretion may mediate
changes in maternal behavior .
24
Relaxin is a hormone thought to act synergistically with
progesterone to maintain pregnancy. It also causes relaxation of
pelvic ligaments at the end of gestation and may therefore aid in
parturition. In some of the species in which relaxin is known to
be produced, it is produced by the placenta, while in others, the
major source is the corpus luteum. In some species, relaxin is
produced by both the corpus luteum and placenta
Since the placenta synthesizes a PTH related protein and appears to regulate PTH-rP
via extracellular calcium levels, it is not unexpected that trophoblasts also secrete
calcitonin, the counterpart to PTH in calcium homeostasis. As with hCG secretion, the
addition of cAMP to placental cultures increased calcitonin secretion.

25. NPY binding to its receptors contributes to
uterine contractility through a pertussis
toxin sensitive G-protein mediated pathway.
This pathway starts from the NPY receptors
and continues with inhibition of adenylate
cyclase activity and increase of intracellular
calcium levels
36 AA in cytotrophoblast increase during labor but
not CS Stimulate CRH secretion from placenta
Placental neuropeptide Y
25
The placenta functions as a systemic pressure regulating
system. The renin and angiotensinogen system is critical for
systemic fluid and pressure homeostasis. In the case of the
kidney, a decrease in renal perfusion leads to an increase in
renin production which triggers a cascade of events to
increase in perfusion of the kidney. Preeclampsia presents
clinically as a systemic increase in maternal BP during
pregnancy. The trigger for this increase appears to be a
decrease in uteroplacental blood flow to the placenta via the
maternal spiral arteries. The signal placenta utilizes to
induce this change is not known, but the finding of renin
within the placenta suggests that this hormone may function
in the placenta much as it does in the kidney.

26. CYTOKINE AND GROWTH FACTORS
• THE PLACENTA IS THE SOURCE OF NUMEROUS GROWTH FACTORS
INCLUDING TRANSFORMING GROWTH FACTORS A AND ß (TGFA, TGFß),
AND EPIDERMAL GROWTH FACTOR (EGF) HAVE BEEN IDENTIFIED IN
TROPHOBLASTS, BOTH IN VITRO AND IN VIVO. TGFß HAS BEEN
IDENTIFIED BY IMMUNOHISTOCHEMISTRY IN FIRST AND THIRD
TRIMESTER HUMAN PLACENTA, ESPECIALLY IN THE SYNCYTIAL
TROPHOBLASTS AND THE CELL COLUMNS OF FIRST TRIMESTER
ANCHORING VILLI. TROPHOBLAST DERIVED TGFß-AS WELL AS DECIDUAL
DERIVED TGFß24-AT THE UTERO-PLACENTAL JUNCTION MAY STIMULATE
THE ANCHORING TROPHOBLASTS TO MAKE TUN22, THE PLACENTAL
FIBRONECTIN FOUND IN THIS LOCATION. INHIBIN, ACTIVIN,
FOLLISTATIN, INSULIN-LIKE GROWTH FACTOR (IGF), EPIDERMAL
GROWTH FACTOR (EGF), FIBROBLAST GROWTH FACTOR (FGF),
PLATELET-DERIVED GROWTH FACTOR (PDGF), AND ANGIOGENIN.EGF
AND THE EGF RECEPTOR HAVE BEEN LOCALIZED TO THE
SYNCYTIOTROPHOBLAST IN INTRAUTERINE AND ECTOPIC
PREGNANCIES, SUGGESTING A POTENTIAL AUTOCRINE ROLE FOR EGF
IN PLACENTAL GROWTH. TGFA, AN EGF-LIKE HORMONE, HAS ALSO
BEEN IDENTIFIED IN THE PLACENTA THROUGHOUT GESTATION, BUT
IN THE CYTOTROPHOBLASTS OF THE CHORIONIC VILLI. BOTH EGF
AND TGFA WERE ABLE TO STIMULATE CULTURED
26
PAPP-A alpha2 750 KD (bind and
inactivates serine protease and heparin
and inhibits lymphocyte transformation)
PAPP-B beta1 1000KD
PSG (20 variant,Ab causes 80 abortion)
PP5 beta1 36
PP10 alpha1 48
Placental type alkaline phosphatase
Leucine aminopeptidase (oxytocinase)
Other placental proteins

27. 27
CLOSELY RELATED DIMERIC GLYCOPROTEIN HORMONES.
1. ACTIVIN IS A HOMODIMER OF TWO INHIBIN ß-SUBUNITS.
THE PLACENTA PRODUCES ALL THREE SUBUNITS: A, ßA AND
ßB,.
2. IN THE NON-PREGNANT STATE INHIBIN IS MADE IN THE
HUMAN TESTIS AND GRANULOSA CELLS OF THE OVARY AND
FUNCTIONS TO INHIBIT FSH RELEASE FROM THE PITUITARY.
3. DURING PREGNANCY, THE MAJOR SOURCE OF INHIBIN
APPEARS TO BE THE PLACENTA. ACTIVIN A ENHANCES THE
PRODUCTION OF PROSTAGLANDINS AND OXYTOCIN IN A
PARACRINE MANNER IN THE PLACENTA.
4. ACTIVIN APPEARS TO STIMULATE TROPHOBLAST HCG
SECRETION, WHILE INHIBIN CAN SUPPRESS HCG SECRETION IN
TERM PLACENTAL EXPLANTS. INTERESTINGLY INHIBIN DOES
NOT APPEAR TO INHIBIT HCG SECRETION IN FIRST TRIMESTER
EXPLANTS, SUGGESTING THAT INHIBIN-ACTIVIN REGULATION
OF HCG MAY EXPLAIN THE LONG PERPLEXING OBSERVATION
THAT HCG SECRETION PEAKS IN THE FIRST TRIMESTER AND
DECREASES THEREAFTER IN SPITE OF THE FACT THAT
TROPHOBLAST MASS CONTINUES TO RISE THROUGHOUT
PREGNANCY.
Activin and Inhibin
Inhibin is a heterodimer of a and ß subunits (which exist as two
distinct peptides: ßA or ßB, inhibin localized within both cyto and
syncytiotrophoblasts, while in situ hybridization for a and ßA subunits
revealed message only in the cytotrophoblasts, suggesting synthesis
occurs in the cytotrophoblast layer followed by transport of finished
product to the overlying syncytium . inhibin has been shown to be
secreted by cultured trophoblasts in vitro, the secretion of which can
be increased by EGF and prostaglandins. The inhibitory action of
follistatin on activin. A1 and A2: Activin interaction with type 2
receptor enhances binding of type 1 receptor and formation of the
active heteromeric receptor. B. Follistatin binds with activin so that
the complex molecule cannot interact with activin type 2 receptor and
the active heteromeric receptor cannot be formatted.

28. IMMUNOLOGICAL ROLE
• SINCE THE FETUS CONTAINS GENETIC MATERIAL FROM BOTH
THE MOTHER AND THE FATHER IT IS SAID TO BE SEMI-
ALLOGENIC FOR THE MOTHER, THIS MEANS THAT THE
MOTHER AND FETUS WOULD HAVE DIFFERENT MAJOR
HISTOCOMPATABILITY COMPLEXES (MHC). THIS SHOULD
MEAN THAT THE FETUS WOULD BE REJECTED IN A FAIRLY
SHORT TIME AS IN A TRANSPLANTATION OR GRAFT, IT
WOULD ALSO MEAN THAT ANY FUTURE FETUS WITH THE
SAME FATHER WOULD BE EVEN MORE QUICKLY REJECTED BY
THE MOTHER. THERE EVIDENCE TO SUGGEST THAT HAVING
DIFFERENT MHC'S IS BENEFICIAL .
• THE MOST IMPORTANT FACTOR IS THE LACK OF BOTH CLASS I
AND CLASS II MHC ANTIGENS ON THE CHORIONIC VILLI, THUS
GIVING THE FETUS PROTECTION AGAINST ALLOGENIC
ATTACK BY THE MOTHERS IMMUNE SYSTEM .IT HAS BEEN
FOUND THAT SOME POPULATIONS OF CYTOTROPHOBLAST
CELLS PRODUCE A UNIQUE CLASS I MHC MOLECULE THAT
HAS BEEN NAMED HLA G. HLA G HAS SOME INTERESTING
PROPERTIES THAT MAY MEAN THAT IT IS AN INTEGRAL PART
OF THE DEFENSE MECHANISM OF THE FETO-PLACENTAL UNIT,
FOR EXAMPLE HLA G TRANSFECTED L CELLS ARE MORE
RESISTANT THAN CONTROL ONES TO NATURAL KILLER CELLS
OR T CELL MEDIATED LYSIS . CYTOKINES SEEM TO BE
IMPORTANT IN POST-IMPLANTATION PREGNANCY GIVEN THAT
BOTH GRANULOCYTE MACROPHAGE-COLONY STIMULATING
FACTOR (GM-CSF) AND TRANSFORMING GROWTH FACTOR-ß
(TGF-ß) ARE PRODUCED BY THE MATERNAL ENDOMETRIUM
28

29. 29
Decidua is the term for the modified mucosal lining of the
uterus (modified endometrium) during a pregnancy, which
forms the maternal part of the placenta. Decidua is formed in a
process called decidualization under the influence of
progesterone. Decidualization is a process that occurs in early
pregnancy. It is an adaption of the uterus to enable
implantation of the embryo. The decidua is shed during the
birthing process.
Decidualization begins in the stromal cells around the
implanted blastocyst, but soon spreads to involve the rest of
the pregnancy endometrium. In humans, blastocyst formation
begins about 5 days after fertilization when a fluid-filled cavity
opens up in the morula, a ball of cells. Endometrial cells
become decidual cells. As the stromal cells enlarge, they
dominate the endometrium and the glandular component
becomes insignificant. Decidual cells are large with ample
cytoplasm, distinct cell borders and small, rounded nuclei. As
the maternal interface to the embryo the decidua participates
in the exchanges of nutrition, gas, and waste with the
gestation. It also protects the pregnancy from the maternal
immune system.

30. 30
after ovulation, in mammals, the endometrial lining becomes transformed into a
secretory lining in preparation of accepting the embryo. Without implantation,
the secretory lining will be absorbed (estrous cycle) or shed (menstrual cycle).
With implantation the lining now termed decidua evolves further during the
pregnancy.
The thickened superficial endometrial layers become the decidua, as follows:
•The endometrium immediately beneath the implantation site, into which the
major trophoblast growth occurs, becomes the decidua basalis
•The thin rim of endometrial stroma overlying the blastocyst becomes the
decidua capsularis
•The endometrium lining the rest of the uterine cavity is called the decidua
parietalis begins in the stromal cells around the implanted blastocyst, but soon
spreads to involve the rest of the pregnancy endometrium. In humans,
blastocyst formation begins about 5 days after fertilization when a fluid-filled
cavity opens up in the morula, a ball of cells. Endometrial cells become decidual
cells. As the stromal cells enlarge, they dominate the endometrium and the
glandular component becomes insignificant. Decidual cells are large with ample
cytoplasm, distinct cell borders and small, rounded nuclei. As the maternal
interface to the embryo the decidua participates in the exchanges of nutrition,
gas, and waste with the gestation. It also protects the pregnancy from the
maternal immune system.
Furthermore, the decidua has to allow a very controlled invasion of the
trophoblast. In invasive placental disorders like placenta accreta decidualization
have been consistently found to be deficient. The decidua is shed during the
birthing process.
The decidua secretes hormones,
growth factors, and cytokines. It has
receptors for estrogen, progesterone,
growth hormone, and others. Among
its products are hormones commonly
associated with other organs such as
cortisol, CRF, GnRH, prolactin, and
relaxin. Decidual prolactin is not under
dopaminergic control. Pregnancy
protein 14 (PP-14), also called placental
protein 12, and Insulin-like growth
factor-binding protein 1(IGFBP1)
appear to be specific products of the
secretory and decidual lining. Other
factors released include interleukin-15
and vascular endothelial growth factor
(VEGF). A reasonable understanding of
the role and interplay of these
hormones and factors has not been
evolved.

31. 31
Different layers of the deciduas have been described:
•a compact outer layer (stratum compactum)
•an intermediate layer (stratum spongiosum)
•a boundary layer adjacent to the myometrium.
That part of the decidua that interacts with the trophoblast is
the decidua vera (“true decidua”). The remainder of the
decidua is termed the decidua parietalis.
The decidua has a histologically-distinct appearance,
displaying large polygonal decidual cells in the stroma. These
are enlarged endometrial stromal cells, which resemble
epithelium (and are referred to as “epithelioid”).
Formation of a specialized decidua is called decidualization,
which is a special property of endometrium seen only in
hemochorial placentation.
Decidualization includes the process of differentiation of the
spindle-shape stromal fibroblasts into the plump secretory
decidual cells, which create a pericellular extracellular matrix
rich in fibronectin and laminin (similar to epithelial cells).
Vascularity, as well as vascular permeability, is enhanced in
the decidualizing endometrium.
Its leukocyte population is distinct,
with the presence of large endometrial
granular leukocytes being
predominant, while polynuclear
leukocytes and B-cells are scant.
The large granular lymphocytes (CD56
bright) are called “uterine NK cells” or
“uNK cells” in mice, and “decidual NK
cells” or “dNK cells” in humans.
The border to the trophoblast is called
Nitabuch’s layer.
Decidua function
The purpose of the decidua is to
impede the invasion of trophoblasts, a
feat it accomplishes not only by
forming the physical barrier but also
by generating cytokines promoting
attachment of the trophoblast.