Placental Physiology
AnS 536
Spring 2015
Primate Placental Development
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Fertilization at ampullar-isthmic junction
It takes four days to reach uterus
During this time, cell divisions have
produced compact clump of cells—morula
Morula is surrounded by zona pellucida
Formation of cavity within cell clump
results in blastocyst
Zona pellucida degenerates (protease,
uteroglobin)
Primate Placental Development
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Blastocyst becomes implanted into
endometrium
Blastocyst consists of:
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Trophoblast layer—single cell layer that makes up
the wall of the blastocyst; forms the placenta
Inner cell mass—aggregation of cells bulging into
cavity; forms the embryo
Primate Placental Development
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Inner cell mass differentiates into hypoblast
and epiblast layers
These form the bilaminar germ disc
Gastrulation occurs during third week—
establishes three germ layers
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Ectoderm, mesoderm, endoderm
Primate Placental Development
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Mesoderm grows to form lining of the
trophoblast by day 15
Chorion—trophoblast with mesoderm lining
Mesoderm extends into villi, forming secondary
stem villi
Fetal blood vessels develop in mesoderm cores
of villi
Vessels connect to fetal circulation, become
tertiary stem villi
Chorion
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Outer membrane
Gradually fuses with allantois during
differentiation (allantochorion)
Inner aspect bounded by outer layer of
amnion
Outer aspect associated with trophoblastic
villi
Composed of connective tissue membrane,
carries fetal vessels
Amnion
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Completely occupies chorionic sac by 12
weeks
Contains amniontic fluid—protects against
shock
Amnion is avascular; in humans, not fused to
chorion
Yolk Sac
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Produces primordial germ cells
Hematopoietic organ
Allantois
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Contributes blood vessels to the placenta
Becomes the umbilical circulation
Forms a pocket for waste products
Umbilical Cord
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Surface lined by amniotic epithelium
Parenchyma composed of Wharton’s jelly
(mucopolysaccharides)
Human umbilical cord has 2 arteries, 1 vein,
cattle have 2 arteries and 2 veins
Vessels divide within the chorionic plate;
establish circulation to terminal villi
Terminal Villi
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Functional units of the human placenta
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First trimester
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Villi large, covered by 2 layers of trophoblast
Inner layer is the cytotrophoblast
Outer layer is the syncytiotrophoblast
Vessels small, centrally located
Terminal Villi
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Second trimester
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Villi 1/3-1/2 diameter as in first trimester
Cytotrophoblast not continuous, difficult to locate
Capillaries are larger, more numerous
Terminal Villi
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Final trimester
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Villi 1.5 times as big as in second trimester
Intervillous space develops into blood sinus
Spaces bound by chorionic plate and deciduas
basalis
Filled with maternal blood, fibrin deposits
Decidua
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Decidua—endometrial portion shed after
parturition
Decidua basalis—decidua between fetal
chorionic sac and basal layer of endometrium
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Chorion frondosum—the most highly
vascularized portion of the chorion
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Becomes maternal part of placenta
Also called the embryonic pole
Becomes associated with deciduas basalis
Basal plate—deciduas basalis and basal layer
of endometrium
Decidua
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Decidua parietalis—lines entire pregnant
uterus, except where placenta forms
Decidua capsularis—portion of the
endometrium superficial to embryo
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Becomes thin, atrophic as embryo develops
Chorion laeve—portion of fetal chorial
associated with abembryonic pole
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Smooth and vascular
Circulatory Patterns
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Four potential arrangements:
Countercurrent
Concurrent
Crosscurrent
Pool-type
Pulsatility is also a factor
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Maternal and fetal heart rates out of phase
Implications for efficiency of transfer, tissue function,
survival
Circulatory Patterns
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In primates
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Maternal tissues eroded above the decidual plate
Geometery resembles crosscurrent flow
~150 mL maternal blood in intervillous spaces
Replenished 3-4 times per minute
Circulatory Patterns
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In other placental types
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Fetal and maternal villi interdigitate
Most evidence supports a disordered
arrangement of vessels
Placental Function
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Endocrine organ
Mediates exchange of metabolic and
gaseous products
Nutrient and electrolyte exchange
Primates—maternal antibodies to fetus
Converts maternal cholesterol to
progesterone
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Important for progesterone synthesis after fourth
month (following luteolysis)
Placental Function
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Estriol synthesis
Estriol—primary estrogen in maternal
circulation during pregnancy
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Contributes to uterine growth, mammary
development
Progesterone
16α-OH-DHEA sulfate
(Fetal Liver)
DHEA
(Fetal Adrenal)
Estriol
(Placenta)
Placentae Differentiation
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Grossly separated into
classifications
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Based upon number of
placental layers that
separate maternal blood
from fetal blood
Classifications
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Differentiated based upon
the distribution of chorionic
villi (functional unit of
placenta)
Distinguished
microscopically into types
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Diffuse
Zonary
Discoid
Cotyledonary
Types
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Epitheliochorial
Syndesmochorial
Endotheliochorial
Hemochorial
Histological Classification
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Based on presence/absence of maternal
tissues
Epitheliochorial—all layers present
Syndesmochorial—maternal surface
epithelium absent
Endotheliochorial—only endometrial vessel
walls present
Hemochorial—vessel walls absent; chorionic
villi bathed in maternal blood
Hemoendothelial—chorionic trophoderm and
maternal tissues absent; fetal capillary
endothelium separates maternal and fetal
blood
Senger, PL. Pathways to Pregnancy
and Parturition. 2nd Ed. 2003
Placentae Differentiation
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Mare and Sow
Diffuse
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Uniform distribution of chorionic villi that cover the
surface of the chorion
Epitheliochorial
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Least intimate of placental types
Endometrial epithelium is directly apposed to the
epithelium of the chorion
Placentae Differentiation
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Dogs and Cats
Zonary
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Have band-like zone of chorionic villi
Endotheliochorial
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Displays endometiral epithelium that has
completely eroded and maternal capillaries are
almost directly exposed to the chorionic
epithelium
Placentae Differentiation
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Rodents and Primates
Discoid
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Display regionalized disc of chorionic villi
Hemochorial
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Most intimate of all placental types
Chorionic epithelium is directly apposed to pools
of maternal blood
Placentae Differentiation
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Ruminants
Cotyledonary
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Numerous, discrete button-like structures (cotyledons)
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Normally 80-120, but can be thousands in microcotyledonary structures
Cotyledons attach at caruncles scattered throughout medial
sides of horns of uterus
Syndesmochorial
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Similar to the epitheliochorial type
Endometrial epithelium constantly erodes and regrows
Maternal capillaries exposed to the chorionic epithelium for
periods of time
O2 Transport Across the Placenta
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Occurs through simple diffusion and
facilitated diffusion (enhanced by cytochrome
P450)
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Difference in partial pressure between maternal
and fetal blood produces simple diffusion
However, kinetics of O2 transport faster than can
be accounted for by simple diffusion
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Cytochrome P450 enhances rate of diffusion
CO2 Transport Across the Placenta
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CO2 only crosses placenta by simple diffusion
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CO2 is more soluble in lipids, diffuses even faster
than oxygen with a minimum gradient
PCO2 is higher in the fetus than in
maternal blood
Expired in the maternal lungs
Nutrient Transport Across the Placenta
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Simple sugars (glucose)
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Transported by facilitated diffusion using specific
carrier molecules (GLUT1) across a concentration
gradient
GLUT1 can transport glucose across the placental
barrier 10,000 times faster compared to diffusion
Glucose is major source of energy for the fetus
Rate of glucose transportation is dependent upon the
amount of glucose in maternal circulation
Fructose is not selectively permeable to placenta
Glucose Transport Across the Placenta
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Maternal levels greater than fetal levels
Newborn concentrations increase rapidly to
adult levels
Extremely low levels are peculiarity of those
species with high fetal fructose
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Low blood glucose concentrations prior to birth
are partly a hypoglycemic effect of fructose
Fructose Transport Across the Placenta
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Site of synthesis is placenta
Placenta is permeable to
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Sucrose
Sorbose
Maltose
Lactose
Fructose
Protein Transport Across the Placenta
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Proteins (amino acids)
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Some transported by facilitated diffusion using
specific carrier molecules
Transport of AA occur on both the fetal and
maternal membranes
Essential amino acids (EAA)
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Some EAA (histidine) are higher in fetal plasma
Active transport across the placenta facilitates this
nutrient transport
Protein Transport Across the Placenta
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Amino acid active transport
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Regulated through transporter protein systems on
both membranes of the trophoblast
Three steps
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Uptake from maternal circulation across the microvillous
membrane
Transport through the trophoblast cytoplasm
Transport out of trophoblast across the basal membrane
into umbilical circulation
Protein Transport Across the Placenta
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Intact maternal proteins
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Do not cross the placental barrier
Fetus synthesizes its own proteins from AA that
were transported to the fetus
Immunoglobulins
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Transported from the dam to fetus through
pinocytosis in a hemochorial or and
endotheliochorial placenta types
Transported very slowly
Fetus cannot synthesize large quantities
Fatty Acid Transport Across the Placenta
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Lipids
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TAGs
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Are transported across the placenta in the form of free fatty
acids (FFAs)
Very low levels of cholesterol and high density lipoproteins
relative to maternal levels
Do not transport across the placenta
Fetus generates its own from maternal FAs
FFAs and glycerol
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Cross the placental barrier at much reduced rates as
compared to glucose and AAs
Maternal Versus Fetal Levels of Main
Metabolic Substrates
Vitamin Transport Across the Placenta
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Vitamins
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Cross the placenta at different rates
Fat soluble vitamins (A, D, and E)
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Do not cross the placenta easily
Vitamin A
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Transports across the placenta in the form of retinol bound
to a specific carrier protein
Vitamin D
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Uses a binding protein for transport across the placenta
Vitamin Transport Across the Placenta
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Water soluble vitamins (B vitamins and vitamin C)
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Cross with relative ease
Ascorbic acid (vitamin C)
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Transported by active transport across a gradient
Vitamin B12
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Receptor-mediated transport as transcobalamin II
Mineral Transport Across the Placenta
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Minerals
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Transported at different rates
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Usually through active transport
Calcium (Ca+)
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Depending upon fetal development
Used to support the fetal skeleton
Is needed in large quantities throughout gestation
Magnesium (Mg)
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Fetal levels are higher than maternal
Mineral Transport Across the Placenta
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Phosphate
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Needed in large quantities during the last trimester of
gestation
Iron (Fe+)
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Increased uptake nearing term
Transferred across a concentration gradient
Some species use carrier transferrin
Placental Energy Sources
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Placenta has high energy demands
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Utilizes glucose as principle source of energy
Maternal glucose and oxygen transported to the uterus
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Placenta consumes ½ of all glucose delivered
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Glucose is converted to lactate and some is oxidized to yield CO2
Lactate is released to fetal and maternal circulation and is used
directly (in the fetus) or indirectly (maternal circulation transports
it back to the liver to be converted to glucose) as an energy
source
Placenta consumes 2/3 of all oxygen delivered
Post-parturition Placental Release
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Placental release from uterine endometrium occurs
at different rates in different species
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Immediate release or up to hours post-parturition
Order of events:
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Contractions begin
Blood flow to fetal and maternal placentomes decrease
Small blood vessels in placentomes shrink
Capillary pressure decreases and separation of the
membranes occur
Post-parturition Placental Release
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Factors leading to retained membranes:
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Any process that causes continual pressure on the attachment
sites of the placenta causing trauma or infection
Failure of the uterus to contract
Rapid closure of the cervix
Non-pregnant uterine horn can trap membranes
Nutritional deficiency (especially selenium, vitamins E and A)
Shortened or prolonged gestation periods
Twins
Cesarian deliveries
Dystocia
Abortions