Placental Development and

Functions

Trainee Obstetrics Programme - 2007

St. Luke’s Teaching Hospital

Development of the Placenta Polar body

Zona pellucida

– Morula [16 cell stage: day 8]

enters uterine cavity and starts to
undergo changes:-
– fluid accumulates in intercellular
spaces between the centrally
placed cells [inner cell mass]
– as fluid volume increases,
spaces on one side become Inner cell mass
confluent to form a single cavity
[blastocyst]
– as blastocyst [day 9] enlarges, it
presses on zona pellucida which
disappears and trophoblast Trophoblast
comes in contact with decidua -->
implantation [day 10-11]

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¾Contact of polar trophoblast to decidua
induces proliferation of the trophoblast
at the embryonic pole.’

¾Primitive Trophoblast differentiates

Inner cell mass
into:
¾Syncytiotrophoblast
¾Cytotrophoblast
¾Hydrolytic enzymes secreted by
trophoblast digest the extracellular
matrix between the endothelial cells to
allow the embryo to penetrate completely
into the decidua.

¾Inner cell mass starts to undergo

morphological changes to form the
¾primitive ectoderm and
¾primitive endoderm.
¾A space appears between the
ectoderm and trophoblast - the amniotic
cavity.
Yolk sac

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 Chorion
fondosum

Chorion
laeve

Decidua
basalis

Decidua
capsularis

Decidua
parietalis

¾Trophoblast develops differentially forming the Chorion fondosum and

Chorion laeve.
¾The uterine decidua similarly forms the decidua basalis and decidua
capsularis. The decidua capsularis eventually fuses with the decidua parietalis.

Syncytial lacunae
[maternal blood]
Syncytiotrophoblast

Cytotrophoblast Fetoplacental tissue

Mesenchyme

Fetal circulation

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 z PLACENTAL SIZE
– 1st trimester: Placenta > fetus
– 12-14weeks: Placenta = fetus
– >14 weeks: Placenta < fetus
z 28 weeks: ratio 1:4
z 40 weeks: ratio 1:7

z Umbilical cord insertions

– Central
– Marginal [battledore]
– Velamentous

z Placental divisions
– Bipartate
– Succenturate

z Membrane arrangement
– Circumvalate

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z Degree of uterine infiltration z Membrane pathology
– Placenta accreta – Chorionamnionitis
– Placenta increta – Amnion nodosum
– Placenta percreta

z Histological pathology z Gross Pathology

– Hydropic degeneration – Perivillous fibrin deposition
– Hydatidiform mole – Subchorionic fibrin plaques
– Chorioncarcinoma – Placental infraction
z Specific infections – Calcification
– Bacterial – Septal cysts
z Listeria, tuberculosis, syphilitic – Haemagiomata
– Fungal – Intervillous thrombosis
z Monilial, coccidiodomycosis, – Fetal artery thrombosis
histoplasmonsis
– Retroplacental haematomata
– Protozoal
– Marginal haematoma
z Toxoplasma, malaria
– Viral
z Variola, vaccinia, varicella, rubella

Liquor production

z <16 weeks gestation mainly an exudate [maternal component]

z >16 weeks main contribution from fetal urine output

CIRCULATION
fetal swallowing GIT Absorption into circulation

Fetal kidneys urine Placenta to mother

Maternal circulation

Amniotic cavity

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Liquor pathology
Polyhydramnios Oligohydramnios
z Maternal causes z Fetal causes [amnion nodosum]
– Twins
– Diabetes mellitus [fetal polyuria] z Renal:- poor urine production
z Placental/cord – IUGR
– Tumours [haemangioma] – Renal agenesis
– Prune belly syndrome
z Fetal causes
z Congestive heart failure [placental
oedema]
– congenital heart disease
– Anaemia, Rh incompatibility
z Problems of swallowing
– Anaencephaly
– Muscular problems
– oesophageal/duodenal atresia
z Exudation
– omphalocoele
z Renal
– Nephrotic syndrome

Functions of the Placenta

z Placenta is a “villous haemo-chorial” organ

z Functions:
– Metabolism
– Hormone production
– Placental transfer
– Haematopoietic
– Immunological

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Placental metabolism

z Rate of metabolism similar to adult liver or kidney.

Oxygen consumption is of same order as that of
pancreas and kidney.
z Placenta performs many synthetic and catabolic
functions.
– Metabolic processes include: active glycolytic cycle, pentose phosphate
pathway, tricarboxylic cycle, electron transmitter systems
z Most substances cross the placenta by active transport -
a mechanism that requires energy expenditure.
z More than 60 placental enzymes have been described.

Placental hormonal production

z Protein [polypeptides] Hormones

– Human Chorionic Gonadotrophin rises in 1st-early 2nd trimester, low
levels after ~16 weeks
z Responsible for fetal adrenal cortex development
– Human Chorionic Somatotrophin fosters embryonic development by
increasing fetal cell glucose absorption and stimulating lipid and CHO
metabolism.
– Human Placental Lactogen rises progressively from about 12 weeks up to
term
z Possibly useful in preparation for lacatation – but contributes to diabetogenic
effects of pregnancy.
– ACTH, TSH, melanocyte stimulating hormone, relaxin, oxytocin,
vasopressin
z All isolated from placental tissue but most likely are of maternal or fetal origin.

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Placental hormonal production

z Steroid Hormones
– all rise progressively to plateau at term
z Progesterone
– Maintains pregnancy, inhibits myometrial activity, increases
mammary growth, antialdosterone effect.
z Oestrogens: mainly oestriol
– Increases uterine growth and vascular supply to decidua and
myometrium, increases metabolism and placental enzyme
systems.
z Androgens, corticosteroids

Placental transfer

z Gaseous exchange [CO2, O2]

– Passive diffusion across a pressure gradient – assisted by maternal
hyperventilation [progesterone effect] and fetal haemoglobin Dissociation curve for
HbF and HbA

Higher saturation
with lower PO2

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 z Nutrient exchange
Placental – [carbohydrates, amino
transfer acids, fatty acids, etc.]
z Electrolytes
z Immunoglobulins
z Drugs
Water, Na+, Cl-, K+

glucose, lactose
[carrier protein]

blood gases, fatty acids, fat

soluble vitamins, steroids

amino acids, iron, calcium

[Na pump]

zVascular breaks
IgG
zPlacental
or fetal cells to
mother
zMelanoma & leukaemic cells
to fetus

Placental haematopoiesis

z Placenta takes up iron, vitamin B12 and folic acid -->

tendency towards anaemia in pregnancy
z Fetal erythropoietin may cross placenta to mother since
maternal reticulocyte counts are elevated in presence of fetal anaemia.
z Influence of placental hormones on maternal haematopoesis
– HPL augments action of erythropoetin
– Oestrogens
z antagonise the HPL effect
z inhibit marrow utilization of erythropoetin
z diminish erythropoetin production
– Progesterone counters oestrogen effects

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 Placental immunology

z Feto-placental unit is an allograft that defies the

foreign body tissue reaction [Type IV cell-mediated
reaction]
– fetus not antigenically mature.
– Non-Specific Unresponsiveness in mother response due to
increased corticosteroids, oestrogen/progesterone, HCG/HPL BUT Type IV
cell-mediated response little effected by hormonal
influences.
– Specific Unresponsiveness by immunological enhancement
utilizing a humeral response to “cover” the antigenic sites
¾Placental Sink Hypothesis

Teratogenesis

z Thalidomide story
– 1953 Synthesis
– 1954 Patent applied for
– 1954-56 Clinical tests
– 1957 Put on market
– 1959 Dysmelia observed
– 1960 Monthly sales 1.4 tons
– 1961 Striking increase in frequency of dysmelia
Exogenous chemical cause suspected.
– Nov. 1961 Thalidomide linked to dysmelia
– Nov. 1961 withdrawn from German market
– Sept 1962 withdrawn from Japanese market

Quick identification and reaction because rate of natural occurrence of

dysmelia is low. Would have been a different matter if:
¾Abnormality occurred at high incidence
¾Multivariate relationships

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 Teratogenesis

z Natural incidence of abnormalities

– 1st trimester: ~50% abnormal - most aborted
– 2-3rd trimester: ~2% major & 4-5% minor
z of which 10-20% may be due to teratogens
z Generally, teratogens in man:
– <20th day gestation
¾ drugs will either kill or not effect fetus
– 3-8th week [organogenesis]
¾ Teratogenicity
– 2-3rd trimester
¾ may effect fetus/neonate physiologically

z Types of teratogens
– Exogenous
z Physical
– Temperature changes, lack of oxygen, mechanical influences, ultrasound, ionizing
radiation, electric current
z Chemical
– Medicaments, poisons
z Biological
– Viruses, bacteria, parasites
– Endogenous
z Maternal body factors
– Metabolic products, hormones, antibodies
z Nutritional states
– Vitamin deficiency, nutritional deficiencies

z Types of teratogenesis
– Structural
– Behavioural [eg smoking retards reading age]
– Transplacental carcinogenicity [eg diethylstilboestrol]
– Fetal growth retrardation [eg. smoking]
– Physiological [eg. iodide causing goitre]

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 Maternal
lethal
Safety Zone zone
Fetal lethal zone
Fetal non-teratogenic
non-lethal zone

Maternal non-lethal zone

Fetal LD50 Fetal T/LD100 Fetal LD100 Maternal LD50 Maternal LD100

™LD50 is the median lethal dose; LD100 is the total lethal dose
™T/LD100 is the relationship between 100% fetal mortality & 100% deformity

z The T/LD100 unfortunately is not a specific constant but has a number

of variables.
z Different drugs
z Substance [in rat] Mat. LD 50 T/LD100
– 6-mercaptopurine 250 25
– 5-fluorouracil 230 30
– Methotrexate 17 0.5
– Cyclophosphamide 40 15
– Methyhydrazine 350 50

z Different species
z Species Lowest thalidomide dose
z to procure teratogenesis
– Man 0.5-1.0 mg/kg/day
– Monkey 10
– Rabbit 30
– Mouse 31 Human studies ideal
– Rat 50 ‰Collecting individual observations
– Dog 100 ‰Retrospective studies
– Hamster 350 ‰Prospective studies
‰Semi-experimental studies

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z Different effects at various stages of pregnancy
•Lethal dose for fetus
•Lowest dose affecting development
in rat model

In Man
24th day Anencephalia
26th day Meningomyelocoele
30th day Oesophagel atresis, renal agenesis
34th day Transposition of vessels
38th day Ventricular septal defects
6th week Syndactylia, diaphragmatic hernia
7th-8th week Duodenal atresia
10th week Omphalocoele, Meckel’s diverticulum
12th week Hypospadias
7th-9th month Cryptorchism
9th-10th month Open ductus arteriosus

z Placental transfer of drugs dependant upon:

– Protein binding
z Protein-bound medications cross with difficulty - e.g. bupivicaine
– Lipid solubility
z highly lipid-soluble drugs cross with ease; water-soluble do not
cross unless actively transported – e.g. vitamins
– Degree of ionization
z highly polar or ionized substances do not cross the placenta readily
– e.g. succinylcholine
– pKa of substance i.e. pH of 50% ionization
z most compounds are weak bases pKa ~ 8.0 thus more ionized in
fetal blood stream [pH fetal blood 7.3 pH maternal blood 7.4] Æ
predisposing to trapping of drug onto fetal side of circulation
– Molecular weight of substance
z <600 cross placenta; >1000 do not cross – vide heparin
– Maternal, placental and fetal metabolism
– Concentration gradient
z hence difference between i/v and i/m administration and effect of
uterine tone

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 The Five Commandments
z “...and the Lord said ‘I shall give the medical profession five
commandments for prescribing drugs to pregnant women.
Whoever shall fail to observe these commandments and damage
the fetus irreparably, shalt suffer brimstone and hellfire for
eternity… and I say to you: All women must be considered
pregnant unless proven otherwise”

– I. Thou shalt not prescribe drugs to pregnant or lactating women

unless absolutely indicated.
– II. Thou shalt have only one thought in mind, that is to do the
maximum good to the mother with the least harm to the fetus.
– III. Thou shalt then prescribe drugs for as short a time and in the
lowest dose possible.
– IV. Thou shalt wherever possible prescribe drugs orally or topically in
preference to systemic injection.
– V. Thou shalt prescribe well established drugs rather than new ones.

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