PLACENTAL

FUNCTIONS

ASSOCIATE PROFESSOR
IOLANDA ELENA BLIDARU
MD, PHD
 PLACENTAL FUNCTIONS

4 main functions
transport
metabolism
endocrine
immunologic

Placenta essential function in the fetal growth and

development.
 PLACENTAL FUNCTIONS
The transport function

ST the maternal - fetal tissue

interface of the transcellular transfer.
a functional maturity after the utero-
placental circulation is established.
The placenta - 2 independent
circulations:
the umbilical circulation + the
uterine circulation
 PLACENTAL FUNCTIONS
The transport function
Types of transfer across the placenta
1. simple diffusion (O2, CO2, anesthetic gases,
water, most of the electrolytes);

2. facilitated transfer (glucose);

3. active transport (aminoacids, calcium);

4. receptor facilitated endocytosis (IgG, iron);

5. membrane disruption (uncommon);

6. ? restrictive diffusion (hypothetical

transmembrane channels).
 PLACENTAL FUNCTIONS
The transport function

Facilitated diffusion
Active transport mediated by protein carriers

Transfer can be modified by:

- maternal nutritionel status
- exercise
- disease diabets mellitus
hypertension
alcoholism
 PLACENTAL FUNCTIONS
The transport function

The syncytiothrophoblast is the site

of transport with substances
moving from the apical membrane,
across the cell wall to the basal
membrane.
 PLACENTAL FUNCTIONS
The transport function

OXYGEN
The mechanism of O2 transport is the
simple diffusion.
The O2 necessary at term is about
20ml/min two thirds are transferred to
the fetus.
The fetus a great capacity of
maintaining the proper O2 necessary +
increased possibilities to extract O2 in
cases of hypoxemia.
HbF has a great affinity for O2.
 PLACENTAL FUNCTIONS
The transport function

CARBON DIOXIDE
The diffusion constant of CO2 is 20 times
higher and facilitated by that for O2
(Haldane effect).
The placenta is highly permeable for CO2.

CO2 is present in the blood in the form of

dissolved gas = carbonic acid (the most
important metabolite produced by the
organism), bicarbonate ion, carbonate ion
and carbaminohemoglobin.
 PLACENTAL FUNCTIONS
The transport function

WATER TRANSFER
Exchange of water - at two main
sites:
- the placenta
- the nonplacental chorion
Severe dehydration or over hydration
major impact on fetal homeostasis
and could lead to fatal consequences.
 PLACENTAL FUNCTIONS
The transport function
CARBOHYDRATE TRANSFER
Glucose - the major energy substrate
transported across the placenta by
facilitated diffusion via hexose
transporters.
Transporter proteins for D-glucose -
isolated from the plasma membrane of
the microvilli of human trophoblasts.
In the glucose transfer control are
involved: the maternal and fetal insulin,
GRH, glucocorticoids, progesterone,
estrogens, HCS (HPL) and concentration
gradients.
 PLACENTAL FUNCTIONS
The transport function
AMINO ACID TRANSFER
Maternally derived amino acids are
transferred by active transport across
placenta and present in the fetal
plasma in larger amounts than in the
maternal plasma.
The exception some Ig

The placental amino acids transfer

through ST
 PLACENTAL FUNCTIONS
The transport function

PROTEINS
Maternal IgG antibodies cross in significant
amounts (IgG has a specific carrier that facilitates
active transport).
Fc receptors (present on ST) perform the transport
of Ig G through a process of pinocytosis.
The IgG1 and IgG3 subclasses are predominante
(the receptor has the greatest affinity for them).
IgG1 crosses earliest in pregnancy and is the
primary Ig transferred before 28 weeks. IgG3
crosses later.
 PLACENTAL FUNCTIONS
The transport function

LIPIDS
Neutral fats (triacylglycerols) do not cross
the placenta but glycerol does.
The LDL particles are taken up by a
process of endocytosis.
Cholesterol is used in progesterone
synthesis.
The concentration of arachidonic acid in
fetal plasma is greater than in maternal
plasma (AA a component of membranes
and an eicosanoid precursor).
 PLACENTAL FUNCTIONS
The transport function
VITAMINS AND MINERALS
The fat-soluble vitamins are transported as
lipoproteins complexes.
The water-soluble vitamins & Ca, Mg
active transport.
The placental transfer of Ca influenced
by: metabolites of vitamin D
parathormone
prolactin
calcitonin
The placental transfer of FE++ receptor
mediated endocytosis.
 PLACENTAL FUNCTIONS
Endocrine function
The placenta is a major endocrine organ.
The placenta synthesizes hormones and
cytokines that have major influences on
ovarian, uterine, mammary and fetal
physiology.

Fetal, placental & maternal compartments

form an integrated hormonal unit

The feto-placental-maternal (FPM) unit

creates the
Endocrine Environment
that maintains and drives the processes of
pregnancy and pre-natal development.
 PLACENTAL FUNCTIONS
Endocrine function
Steroid Hormones:
1- Estrogens
2- Progesterone

Protein hormones:
1- Human chorionic gonadotrophin (hCG)
2- Human placental lactogen (hPL)
3- Human chorionic thyrotrophin (hCT)
4- Hypothalamic and pituitary like
hormones
5- Others: inhibin, relaxin and beta
endorphins.
 Estrogens in ovary

The two-cell-two gonadotropin principle

of ovarian steroid hormone production.
1. During the follicular phase - luteinizing
hormone (LH) controls theca cell production of
androstenedione, which diffuses into the adjacent
granulosa cells and acts as precursor for E2
biosynthesis.
The capacity for the granulosa cell to convert
androstenedione to E2 is controlled by follicle-
stimulating hormone (FSH).
 Estrogens in ovary
2. After ovulation, the corpus luteum forms and
both theca-lutein and granulosa-lutein cells
respond to LH. The theca-lutein cells continue to
produce androstenedione, whereas granulosa-
lutein cells greatly increase their capacity to
produce P and to convert androstenedione to E2.

If pregnancy occurs, the production of hCG by the

placenta rescues the corpus luteum.
Estrogens
 PLACENTAL FUNCTIONS
Endocrine function

Estrogens
Synthesized by syncytiotrophoblast from their
precursors:
1. dehydroepiandrosterone sulphate (DHES)
2. 16 -hydroxy dehydroepiandrosterone sulphate
(16 - OH- DHES).

90% of 16 - OH DHES (dehydroepiandrosterone

sulphate ) is derived from fetal origin
(hydroxylation of DHES in the fetal liver).
10% 16 - OH - DHES is derived from the mother (by
the same way).

It is transformed in the placenta into estradiol -

17b (E2).
Estrogens and progesterone
 PLACENTAL FUNCTIONS
Endocrine function

Estrogens
Maternal urinary and serum estriol
important index for fetal wellbeing as

its synthesis depends mainly on the integrity of

the fetal adrenal and liver as well as the
placenta.
(feto - placental unit)

Estrogens are excreted (90%) in the maternal

urine as estriol (E3).
Urinary estriol increases as pregnancy advances
to reach 10-14 mg / 24 hours in late pregnancy.
Schematic presentation of the biosynthesis of
estrogens in the human placenta
Dehydroepiandrosterone sulfate
(DHEA-S), secreted by the fetal
adrenal glands, is converted to 16
-hydroxydehydroepiandrosterone
sulfate (16 OHDHEA-S) in the fetal
liver.
These steroids, DHEA-S and 16
OHDHEA-S, are converted in the
placenta to estrogens, that is, 17
-estradiol (E2) and estriol (E3).
Near term, half of E2 is derived
from fetal adrenal DHEA-S and half
from maternal DHEA-S. On the
other hand, 90 percent of E3 in
the placenta arises from fetal 16
OHDHEA-S and only 10 percent
from all other sources.
 PLACENTAL FUNCTIONS
Endocrine function
P rincip a l biological effects of placental
estrogens
s timulate growth of the myometrium
antagonize the myometrial-suppressing activity of P
s timulate mammary gland development
control over the synthesis and secretion of some
proteins during the first trimester
the cervical ripening
in late gestation induces: myometrial oxytocin
receptors, myometrial gap junction stimulation,
stimulation of the synthesis and release of PG and
contractile proteins, stimulation over the membrane
permeability and on the myometrial electric activity
(preparing the uterus for parturition).
 PLACENTAL FUNCTIONS
Endocrine function

Progesterone
It is synthesized by syncytiotrophoblast
from the maternal cholesterol.
Estrogens, PG, some growth factors
increase P synthesis.
synthesis
Excreted in maternal urine as
pregnandiol.
 PLACENTAL FUNCTIONS
Endocrine function

Progesterone
Roles of P in maintaining pregnancy:
a local immune protection role;

a role in the development of the

placental tissue and in the increase of
placental vasculature;
inhibition of myometrial contractility.
 Changes in concentrations of
progesterone and estrogens in the
maternal serum of humans through
gestation.
 PLACENTAL FUNCTIONS
Endocrine function
Human chorionic gonadotrophin
(hCG)
It is a glycoprotein produced by the
syncytiotrophoblast.
It supports the corpus luteum in the first 10
weeks of pregnancy to produce E2 and P
until the syncytiotrophoblast can produce
them.
HCG molecule composed of 2 subunits:
a. Alpha subunit - similar to FSH, LH, TSH.
b. Beta subunit - specific to hCG.
 PLACENTAL FUNCTIONS
Endocrine function
Human chorionic gonadotrophin
(hCG)
HCG - determined in urine, beginning with the
45th day of gestation.
In the 5th-6th weeks peak values indicate a
normal pregnancy (in evolution).
low valuesectopic pregnancy
interruption of intrauterine pregnancy
HCG rises sharply after implantation, reaches a
peak of 100.000 mIU/ml about the 60-th day of
pregnancy (w 5-6).
HCG falls sharply by the day 100 and is
maintained at this level until term
 PLACENTAL FUNCTIONS
Endocrine function
Human placental lactogen
(HPL)
(chorionic somatomammotropin)
It is a polypeptide hormone produced by the
SC.
The actions of hPL
a. Lipolysis : increasing free fatty acids -
provide a source of energy
b. Inhibition of gluconeogenesis : spare
both glucose and protein - the anti-insulin
effect of hPL.
c. Somatotrophic : fetal growth promotion.
d. Mammotropic and lactogenic effect.
 PLACENTAL FUNCTIONS
Endocrine function
Human placental lactogen
(HPL)
(chorionic somatomammotropin)
HPL - detected by the 5-6th week of
pregnancy, rises steadily until the 36th
week to be 6 mg/ml.
HPL values - one of the best criteria to
watch the evolution of pregnancy in the
third trimester.
Low levels - fetal distress, IUGR,
intrauterine death, chronic placental
insufficiency (serial measurements).
screening test
 PLACENTAL FUNCTIONS
Endocrine function
Hypothalamic and pituitary - like hormones
1. Gonadotropin releasing hormone (GnRH)
2. Corticotropin releasing hormone (CRH)
3. Growth hormone releasing hormone (GH)
4. Proopiomelanocortin derived peptides: ACTH,
Melanocyte stimulating hormone, (MSH), Beta
endorphins and lipotrophins
5. Neurohypophyseal peptides: OXT,
Argininevasopressine (AVP)
6. Growth factors: EGF, insulin and insulin-like growth
factors (IGF I, IGF II)
7. Inhibin, Activin, Relaxin
 SRAA in pregnancy
RENIN, ANGIOTENSIN II, AND PLASMA
VOLUME
The renin-angiotensin-aldosterone axis is
intimately involved in renal control of blood
pressure via sodium and water balance.
Renin is produced by both the maternal
kidney and the placenta
Increased renin substrate =
angiotensinogen is produced by both
maternal and fetal liver.
 SRAA in pregnancy

Nulliparas who remained normotensive

became and stayed refractory to the

pressor effects of infused angiotensin II.
Conversely, those who ultimately became

hypertensive developed, but then lost, this

refractoriness. The vascular responsiveness
to angiotensin II is progesterone related.
 PLACENTAL FUNCTIONS
Placental immunological phenomena
The placenta functions as an
immunological barrier between the
mother and the fetus.

Trophoblast is the contact zone between

the maternal tissues and embryo-fetal
structures.

The trophoblast membranes are not

immunologically inert.
inert

The maternal immune system facilitates

the fetal semiallograft.
 PLACENTAL FUNCTIONS
PLACENTAL IMMUNOLOGICAL
PHENOMENA

Trophoblast antigens

They may be grouped into 3 categories:

major histocompatibility complex antigens
(MHC) = HLA

antigens with suspected functions (trophoblast

lymphocyte cross-reactive antigens TLX,
transferrin, the major basic protein)

antigens with unknown functions.

 PLACENTAL FUNCTIONS
PLACENTAL IMMUNOLOGICAL PHENOMENA
The immunological processes in pregnancy
is related to the presence of cytokines in
the MPF unit.

interleukins, and
TNF and interferons

The placenta may have an immunoregulatory

role as demonstrated by the release of
factors that suppress lymphocyte
activation.

Cytokines major mediator in the

immunological phenomena of pregnancy.
 IMMUNOGENICITY OF THE
TROPHOBLASTS
The placenta - considered immunologically
inert and therefore unable to create a
maternal immune response.
MHC class I and II antigens are absent from
villous trophoblasts, which appear to be
immunologically inert at all stages of
gestation.
Invasive extravillous cytotrophoblasts do
express MHC class I molecules: HLA-C, HLA-
E and HLA-G.
 UTERINE NATURAL KILLER CELLS

Normal implantation depends on controlled

trophoblastic invasion of maternal decidua and spiral
arteries. Such invasion must proceed far enough to
provide for normal fetal growth and development, but
there must be a mechanism for regulating its depth.
The uterine decidual natural killer cells (uNK cells)
combined with the unique expression of the 3
specific HLA class I genes in extravillous
cytotrophoblasts act in concert to permit and
subsequently limit trophoblast invasion.
These uNK cells secrete large amounts of TH2 -
cytokines.