Download Chapter 6 Histology of the Chorionic Villi, Fetal Membranes, and

Chapter 6
Histology of the Chorionic
Villi, Fetal Membranes, and
Umbilical Cord
Histology of the Chorionic Villi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Syncytiotrophoblast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Villous Cytotrophoblast (Langhans’ Cells) . . . . . . . . . . . . . . . . . . . . .
Villous Stroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fetal Villous Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Structure and Histology of the Fetal Membranes . . . . . . . . . . . . . . . . .
The Amnion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Amniotic Fluid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chorion Laeve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Trophoblast Layer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Decidua . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Structure and Histology of the Umbilical Cord . . . . . . . . . . . . . . . . . . .
Umbilical Vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Selected References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Histology of the Chorionic Villi
The chorionic villi are the site where virtually all maternofetal and fetomaternal exchange takes place. In fact, most metabolic and endocrine activities of the placenta are localized there as well. The villi are the only
components of the placenta that have a dual blood supply from both
the fetal and maternal circulations. Despite the diversification of villous
types, all chorionic villi exhibit the same basic structure (Figure 6.1). They
are covered by syncytiotrophoblast, an epithelial surface layer (Figure
6.1 A) that is in direct contact with the maternal blood and functions
as an endothelium. Between syncytiotrophoblast and the basement
membrane are the villous cytotrophoblast, or Langhans’ cells. These
are the stem cells of the syncytium, supporting its growth and regeneration. The trophoblastic basement membrane separates the trophoblast
from the villous stroma. The stroma is composed of connective tissue
cells, connective tissue fibers, ground substance, and fetal vessels. In the
larger stem villi, the vessels are mainly arteries and veins, while in the
peripheral branches most fetal vessels are capillaries or “sinusoids.”
The human placenta is hemochorial in that the maternal blood has
Histology of the Chorionic Villi
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Figure 6.1. Morphology of human placental villi. (A) Simplified light microscopic section of two terminal villi, branching off a mature intermediate villus (right). (B) Schematic electron-microscopic
section of the placental barrier, demonstrating typical layers. (Modified from Kaufmann P. Vergleichend-anatomische und funktionelle Aspekte des Placenta-Baues. Funkt Biol Med 1983;2:71–79, with
permission.)
direct contact with trophoblast. The layers separating maternal from
fetal blood are these (Figure 6.1 B):
•
•
•
•
•
•
Syncytiotrophoblast,
An incomplete layer of cytotrophoblast,
The trophoblastic basement membrane,
Connective tissue,
The endothelial basement membrane, and
The fetal capillary endothelium.
Syncytiotrophoblast
The syncytiotrophoblast is a continuous, normally uninterrupted layer
that extends over the surfaces of all villous trees and villi as well as
over parts of the inner surfaces of chorionic and basal plates. It thus
lines the entire intervillous space and is a single continuous structure for
every placenta. Therefore, terms such as “syncytial cells” and “syncytiotrophoblasts,” which are often used, are inappropriate and should
be avoided. Their use indicates a misunderstanding of the true nature
of the syncytiotrophoblast. The syncytium is involved in complex, active
maternofetal transfer mechanisms, including catabolism and resynthesis
of proteins and lipids, synthesis of hormones such as human chorionic
gonadotropin, human chorionic somatotropin, human placental lacto-
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Chapter 6 Histology of the Chorionic Villi, Fetal Membranes, and Umbilical Cord
gen, and human growth hormones, diffusional transfer of gases and
water, the facilitated transfer of glucose, and active transfer of amino
acids and electrolytes.
The syncytium is composed of two plasmalemmas with an intermediate layer of syncytial cytoplasm. It varies in thickness from 2 to
about 10 mm (Figure 6.2). The syncytiotrophoblast at the villous surface
is nearly completely covered by microvilli forming an enormous
maternofetal contact zone that multiplies the total villous surface area
by a factor of 7.67 at term. Remnants of syncytial fusion such as fragments of cell membranes and desmosomes are sometimes present in
the cytoplasm. On routine tissue sections of first trimester placentas
(Figure 6.3), the syncytiotrophoblast appears as a single layer surrounding the cytotrophoblast with no cell border. The nuclei are small,
with moderately dense chromatin. The cytoplasm is homogeneous to finely
Figure 6.2. Simplified drawing of a cross section of a terminal villus demonstrating the structural variability of the syncytiotrophoblast. (a) Vasculosyncytial membrane. (b) Thin syncytial lamella covering villous cytotrophoblast. (c)
Syncytiotrophoblast with well-developed rough endoplasmic reticulum. (e)
Syncytiotrophoblast with well-developed smooth endoplasmic reticulum. (e)
Syncytial knot. (f) Syncytial sprout. (From Kaufmann P, Schiebler ThH, Biobotaru C, Stark J. Enzymhistochemische Untersuchungen an reifen menschlichen
Placentazotten. II. Zur Gliederung des Syncytiotrophoblasten. Histochem
1974;40_191–207, with permission.)
Histology of the Chorionic Villi
Figure 6.3. Light microscopic appearance of a first trimester chorionic villus
with relatively thick syncytiotrophoblast and well-defined cytotrophoblastic
layer. H&E. ¥100.
granular, somewhat basophilic, and is often vacuolated. Later in pregnancy,
the syncytiotrophoblast (Figure 6.4) has a variable thickness as it surrounds the villous structures. Focally, it is thinned to almost invisibility, forming the vasculosyncytial membrane (see Figure 6.2 a), in other
areas it appears as a single layer of cells, while in still other areas, the
nuclei are piled up forming syncytial knots (Figure 6.2 e). The nuclei
Figure 6.4. Light microscopic appearance of third trimester chorionic villi with
irregularly thinned syncytiotrophoblast and focally incomplete cytotrophoblastic layer. H&E. ¥100.
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may focally show degenerative change. Mitotic figures are not identified in syncytiotrophoblast.
Syncytial Knots, Sprouts, and Bridges
Syncytial knots, sprouts, and bridges are names for a heterogeneous
group of syncytiotrophoblastic specializations characterized by a group
of aggregated nuclei at the trophoblastic surface. The general term syncytial knots is often used to refer to this entire group as they are often
indistinguishable on light microscopy. Most commonly, accumulations
of syncytial nuclei in sections of placental villi are the result of tangential sectioning across syncytiotrophoblastic surfaces. For these accumulations, “syncytial knots” is the most appropriate term (Figure 6.4).
Throughout the first half of pregnancy, a limited number of true syncytial sprouts or trophoblastic sprouts (Figure 6.5) can be found. These
are characterized by a vermiform extension from the villous surface
with loosely arranged, large ovoid syncytial nuclei at the tip. Toward the
villous stroma, portions of villous cytotrophoblast and connective
tissue may also be present. These are true proliferative outgrowths of
the chorionic villi. A minority of “syncytial knots” show apoptotic
changes and are the sites of shedding of apoptotic nuclei into the maternal circulation. For these, the term “apoptotic knots” is recommended.
Apoptotic knots are characterized by densely packed nuclei with
condensed chromatin and occasional degenerative change, separated from each
other by slender strands of cytoplasm. The surrounding cytoplasm also
usually exhibits degenerative changes. These apoptotic knots are eventually pinched off together with some surrounding cytoplasm. Syncytial bridges are uncommonly seen. They are true bridges and develop
Figure 6.5. Placental villi from sixth week PM (after last menstrual period). Below is a large mesenchymal villus with several true syncytial sprouts protruding into the intervillous space. At the tips,
they consist only of syncytiotrophoblast, but at the base there is cytotrophoblast and even loose connective tissue. ¥390.
Histology of the Chorionic Villi
from fusion of adjacent villi. Fetal vessels may be identified within
these bridges, connecting the circulations of the two villi.
Generally, in the young placenta, most syncytial knots are attached
to immature intermediate and mesenchymal villi and are signs of
villous sprouting and thus villous growth; less often are they sites of extrusion of apoptotic nuclei. Only a minority of these are due to tangential
sectioning. In contrast, in the mature placenta, the vast majority of
knots are caused by tangential sectioning (see Chapter 18). Far fewer
are accumulations of apoptotic nuclei, and only a very small minority
represents true villous sprouting.
Villous Cytotrophoblast (Langhans’ Cells)
The Langhans’ cells or villous cytotrophoblastic cells form a second
trophoblastic layer beneath the syncytiotrophoblast. During early pregnancy, this layer is nearly complete (Figure 6.3), and later it becomes
discontinuous (Figure 6.4). As the villous surface expands, the cytotrophoblastic cells become widely separated, and so are less numerous
in sectioned material. During all stages of pregnancy, Langhans’ cells
have the characteristic features of undifferentiated, proliferating stem
cells. On light microscopy (Figures 6.3, 6.4), they generally are cuboidal,
polyhedral, or ovoid cells with well-demarcated cell borders, and large, lightly
staining nuclei containing finely dispersed chromatin. The cytoplasm is
usually clear to slightly granular and somewhat basophilic. In contrast
to syncytiotrophoblast, mitotic figures are occasionally found.
Villous Stroma
The trophoblastic basement membrane separates the trophoblastic
epithelium from the villous stroma. Under normal conditions the
average thickness of the trophoblast basement membrane ranges from
20 to 50 nm and consists of collagen IV, laminin, heparan sulfate, and
fibronectin. The amount of collagen varies with villous type. The fixed
connective tissue cells form a network that enmeshes the connective
tissue fibers, free connective tissue cells (Hofbauer cells), and fetal vessels. The
stroma forms a supportive matrix for the cytotrophoblast and, where
the latter is lacking, for the syncytiotrophoblast. Another important
function is a filtration barrier between maternal and fetal circulations.
Mesenchymal cells, or undifferentiated stromal cells, are the prevailing cell type until the end of the second month. In later pregnancy,
they are generally found only in stem villi and in the few remaining
villous precursors, that is, mesenchymal villi and immature intermediate villi (see Chapter 7). They are small spindled cells with little cytoplasm, measuring 10 to 20 mm long and 3 to 4 mm wide (Figure 6.6).
Throughout pregnancy they continue to proliferate and may be found
beneath the trophoblastic surface of large-caliber villi.
At the end of the second month, dramatic changes in stromal architecture and composition take place. Starting in the centers of the villi
and spreading toward the surface, the mesenchymal cells differentiate
into fibroblasts. The newly formed fibroblasts have elongated, bizarreshaped cell bodies that measure about 20 to 30 mm in length. From the cell
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Figure 6.6. Immature chorionic villus with several typical undifferentiated
mesenchymal cells present underneath the trophoblastic cover. H&E. ¥400.
bodies, several long, thin, branching cytoplasmic processes extend
forming flat sails of cytoplasm. These form the stromal channels of the
immature intermediate villi (see Figures 7.1, 7.4, pages 97, 101). Fetal
vessels and connective tissue fibers are present in the spaces between the channels. Later in pregnancy the mesenchymal cells differentiate into myofibroblasts. The myofibroblasts have abundant cytoplasm and are 30 to
100 mm long by 5 to 8 mm wide. In contrast to the fibroblasts, they have
only few short, filiform, or thick processes. The myofibroblasts are arranged
parallel to the longitudinal axis of the villi, and in large stem villi they
form a clearly defined perivascular contractile sheath. Contraction of
these cells may be important for villous turgor, thus influencing the
width of the intervillous space and regulation of maternal intervillous
blood pressure.
Most free connective tissue cells of placental villi are tissue
macrophages, the Hofbauer cells. However, there are a few mast cells
and plasma cells. Hofbauer cells are numerous in both the villous
stroma and the chorionic plate throughout pregnancy. Initially, they are
derived from chorionic mesenchymal cells, but once fetal circulation is
established, they likely derive, as other macrophages do, from fetal
bone marrow-derived monocytes. They share with other macrophages
the expression of surface immunoglobulin receptor and the expression
of major histocompatibility complex, class II antigens. On microscopic
examination (Figure 6.7), Hofbauer cells are large, isolated cells that
vary from 10 mm to 30 mm in diameter. They are round, ovoid, reniform,
or stellate in shape and have an eccentric nucleus. Early in pregnancy,
Histology of the Chorionic Villi
the cytoplasm is coarsely vacuolated; later it is more granular. At term,
Hofbauer cells are difficult to identify and to differentiate from other
cells, in part because they become compressed by the condensing
villous stroma. Villous edema actually “unmasks” the Hofbauer cells,
making them easier to appreciate. The placenta lacks a lymphatic
system to return proteins from the interstitial space to the vascular
system, and therefore the Hofbauer cells are involved in water balance.
They also have a role in maintaining host defenses.
Fetal Villous Vessels
Extraembryonic mesenchyme invades the villi and forms the villous
stroma. Hemangioblastic cells differentiate locally from these cells. Initially, they form cords of cells connected by primitive tight junctions.
Then capillary sprouts, without blood cells, develop at around 21 to 22
days PC (post conception). Intercellular clefts appear and form the
early capillary lumen. Then, around day 28 PC, the first hematopoietic
stem cells develop by delamination from the primitive vessel wall into the early
lumen. At the same time, some of the cells attached to the endothelial
cells on the abluminal side acquire the characteristics of pericytes. A
complete endothelial basement membrane between the endothelial
cells and pericytes is not observed until the third trimester. In stem
vessels and vessels of the chorionic plate, elastic lamina are largely absent,
the muscular coats are thinner, and the muscle cells are more dispersed
than in corresponding vessels of other organs.
Figure 6.7. H&E stained section of an immature chorionic villus with
prominent Hofbauer cells (arrows). ¥400.
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Structure and Histology of the Fetal Membranes
The term “membranes” is usually taken to be synonymous with the
amnion and the chorion laeve of the extraplacental membranes. They
are distinct from the chorion frondosum, which refers to a specialized,
thickened part of the membranes, otherwise known as the placental
disk. The membranes are the “bag of waters” in which the fetus is
enclosed. Their structure and function include turnover of water and
enzymatic activity during the initiation of labor. The structure of the membranes remains constant from the fourth month until term. The mean
thickness after separation from the uterine wall is about 200 to 300 mm,
but because of local edema of the amnionic mesoderm, considerably
thicker membranes are sometimes observed. After birth, the following
layers can be seen histologically (Figure 6.8):
• Amnion
䊊 Amnionic epithelium (20 to 30 mm)
䊊 Amnionic mesoderm (15 to 30 mm)
䊏 Basal lamina or basement membrane
䊏 Compact stromal layer
䊏 Fibroblast layer
• Intermediate spongy layer (highly variable in thickness)
Figure 6.8. Detailed drawing depicting the layers of the fetal membranes. Drawing is not to scale.
Structure and Histology of the Fetal Membranes
• Chorion laeve
䊊 Chorionic mesoderm (15 to 20 mm)
䊏 Blood vessels
䊏 Basal lamina or basement membrane
• Trophoblast (10 to 50 mm) and
• Decidua capsularis (up to 50 mm)
The Amnion
Macroscopically, the amnion is a translucent structure, easily separated
from the underlying chorion. It never truly fuses with the chorion, cellularly speaking, as it is only passively attached by the internal pressure
of the amniotic fluid. It is important to recognize that the amnion does
not possess its own blood vessels and obtains its nutrition and oxygen from the
surrounding chorionic fluid, amniotic fluid, fetal surface vessels, and, during
early gestation, from the magma reticulare. The amnionic epithelium
is derived from the fetal ectoderm and is thus contiguous over the
umbilical cord and fetal skin. The epithelium is composed of a single
layer of flat, cuboidal to columnar cells. Taller, columnar cells are usually
present near the insertion of the membranes at the placental margin,
whereas flatter cells are generally present in the periphery. Defects in
the epithelial layer may be due to expulsion of dying cells into the amniotic fluid. The amnionic epithelium rests on a basement membrane,
which is connected to a thin connective tissue layer by filamentous
strands (see Figure 6.8). The latter consists of a compact stromal layer
and a fibroblast layer. The compact stromal layer contains bundles of
collagen and scattered elastic fibers. The fibroblast layer consists of a
network of fibroblasts and a few macrophages (Figure 6.8). Although
the amnionic mesoderm is divided into a compact stromal layer and
fibroblast layer, these are difficult to appreciate on histologic section.
The amnion has multiple functional roles in the placenta. It is essential for the structural integrity and junctional permeability of the membranes, serving as a permeability barrier to anionic macromolecules. It is
thought to have a role in the onset of labor including the initiation and
maintenance of uterine contractions. The amnion is also involved in the
turnover of the amniotic fluid including resportion and secretory activity. It
also appears to be responsible for regulating the pH of the amniotic fluid
and thus is involved in fetal pH regulation because the fetus delivers
considerable amounts of proteins and bicarbonate via its kidneys into
the amniotic fluid.
Amniotic Fluid
The amniotic fluid is derived from multiple sources: filtration from fetal
blood via the chorionic plate, the umbilical cord, and the fetal urine,
secretory processes of the amnionic epithelium, filtration from maternal
blood via the parietal decidua and the chorion laeve, and filtration from
intracorporeal fetal vessels via the fetal skin in early pregnancy. The amniotic fluid is resorbed by the fetal digestive tract, the amnion, pressuredependent fetomaternal filtration across the membranes, and inhalation. The
volume of the fluid varies with the stages of pregnancy with the
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Table 6.1. Constituents of amniotic fluid
Componenta
Concentration
Glucose
5–20 mg/100 mL
Specific components
Proteins
a1-Albumin, a2-albumin, b-globulin, t-globulins (IgA, IgG,
IgM), a1-fetoprotein, lipoproteins
Lipids
Cholesterol, triglycerides, diglycerides, free fatty acids,
phospholipids
Urea
20–40 mg/100 mL
Hormones
Progesterone, estradiol, estriol, testosterone, aldosterone,
cortisol, thyroid hormones, parathyroid hormone, oxytocin,
glucagons, insulin, hypothalamic-releasing hormones, and
neurophysin
Gonadotropins
Luteinizing hormone, follicle-stimulating hormone,
human chorionic gonadotropin, human placental lactogen,
prolactin, adrenocorticotropic hormone, growth hormone,
somatomedin, and thyrotropin
Enzymes
Activators and inhibitors of proteases such as tissue-type
plasminogen activator, urokinase-type plasminogen
activator, and their respective inhibitors PAI-1 and PAI-2
Cells
Miscellaneous
a
Increase
throughout
pregnancy
Anucleate squamous cells, nucleated squamous cells
(probably from fetal mucous membranes or the amnion),
fetal urothelial cells (both mononuclear and multinuclear)
Amino acids, creatinine, bilirubin
Also present are amino acids, uric acid, creatinine, and bilirubin.
maximum volume of 984 ml at about 33 to 34 weeks. At term, the mean
is 836 ml while at 42 weeks the mean is 544 ml. The pH is around 7.10
and the osmotic pressure is about 255 mosmol. The constituents of the
amniotic fluid are listed in Table 6.1.
Chorion Laeve
The chorionic membrane is a tough fibrous layer carrying the fetal blood
vessels. The amnion and chorion are easily separated and will readily
slide along one another. This is due to the existence of the spongy layer,
which is the result of incomplete fusion of the amnionic and chorionic
mesoderm and is thus between the two layers. It is composed of
loosely arranged bundles of collagen fibers with a few scattered fibroblasts,
separated by a communicating system of clefts (Figure 6.8). Fibroblasts,
macrophages, or remainders of amnionic and chorionic mesothelium
occasionally line the clefts. The collagen composition of both amnion
and chorion contributes to the mechanical stability and tensile properties of the membranes.
The spongy layer continues without sharp demarcation into the next
layer, the chorionic mesoderm. Its composition is similar to the fibroblast layer of the amnion, as it consists of a coarse network of collagen
bundles intermingled with finer argyrophilic fibrils. Fibroblasts, myofibroblasts, and macrophages are also regular findings (Figure 6.8). Chorionic
Structure and Histology of the Fetal Membranes
vessels are present in the mesoderm of the chorionic plate. Occasional
remnants of atrophied chorionic villi may also be found. These former
villi appear as round “balls” of loose connective tissue, without a
trophoblastic cover (Figure 6.9). Finally, there is a basal lamina that is
highly variable in thickness and structure.
Trophoblast Layer
A highly variable layer of trophoblastic cells persists until term. These
cells are the residues of the former villi of the chorion frondosum, intermingled with the trophoblastic residues of the primary chorionic plate
and the trophoblastic shell. They constitute a population of extravillous
tropohoblastic cells that are not involved in implantation, commonly
referred to as migratory trophoblast (see Chapter 8, Extravillous
Trophoblast, Invasive Phenotype). Proliferating, small, undifferentiated
trophoblast may be present as well as nonproliferating, large, differentiated
trophoblast. With advancing gestation, some of these cells may show
degenerative change and foci of fibrinoid (see Chapter 8) are often
observed between the cells. Toward the uterine wall, the trophoblast interdigitates intensely with the decidua.
Decidua
The decidual layer is the only maternal component of the membranes.
The decidual tissue attached to the membranes after birth is largely
Figure 6.9. Macroscopic appearance of normal “membranes.” The amnionic
epithelium (at the left)sits on a thin layer of connective tissue that is not easily
discernible from the chorionic connective tissue. The following layer of extravillous trophoblastic cells contains an atrophic or “ghost” villus. At the right of
the figure is the decidua capsularis with maternal vessels visible. H&E. ¥200.
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Chapter 6 Histology of the Chorionic Villi, Fetal Membranes, and Umbilical Cord
derived from the parietal and capsular decidua (see Figure 5.3, page
76). Whether the individual cells are derived from one or the other layer
cannot be distinguished. The deeper layers of the parietal decidua,
which remain in utero, are richly supplied with maternal blood vessels.
In the superficial parts of the decidua, maternal vessels are the exception. Generally, only a few capillaries, smaller arterioles, and venules can be
identified (Figure 6.9). Macrophages, lymphocytes, and other inflammatory cells may also be present. At the edge of the placenta, the
decidua capsularis is contiguous with the decidua basalis and delimits the “marginal sinus” (see Chapter 8).
Structure and Histology of the Umbilical Cord
The umbilical cord contains two arteries and a vein suspended in
Wharton’s jelly. The surface of the cord consists of a layer of amnionic
epithelium, which is contiguous with the surface of the placenta and
the fetal skin. The amnionic epithelium, near the umbilicus, is largely
unkeratinized, stratified squamous epithelium. This layer provides a transition to the keratinized stratified squamous epithelium of the abdominal wall. Farther away from the umbilicus, the epithelium becomes
stratified columnar epithelium (two to eight cell layers) and finally simple
columnar epithelium as it continues onto the fetal surface. The basal cells
of the stratified portions resemble the epithelium of the membranes,
whereas the superficial cells sometimes are squamous and are occasionally pyknotic. The amnion of the cord is structurally similar to that
described in the membranes, the one difference being that the amnion
of the membranes is easily detached whereas the amnion of the cord grows
firmly into the central connective tissue core and cannot be dislodged.
The connective tissue of the cord is derived from the extraembryonic
mesoblast. The jelly-like material of Wharton’s jelly is composed of a
ground substance (collagen, laminin, heparan sulfate, hyaluronic acid,
carbohydrates with glycosyl and mannosyl groups) distributed in a fine
network of microfibrils. Extracellular matrix molecules are often accumulated around “stromal clefts.” The clefts should not be misinterpreted as lymphatic vessels, which do not exist in the cord or in the
placenta, nor should they be confused with pathologic changes such as
edema or cyst formation (see Chapter 15). The stromal spaces together
with the surrounding meshwork of contractile cells serve as a mechanism for turgor regulation of the cord, avoiding compression of umbilical veins and counteracting bending or kinking of the cord. The cord
is sparsely cellular (Figure 6.10). There are a few macrophages and
somewhat greater numbers of mast cells. Myofibroblasts are present
around vessels and underneath the cord surface.
Umbilical Vessels
There are normally two arteries and one vein in the human umbilical
cord (Figure 6.10). Originally, two veins are present, but the second
normally atrophies during the second month of pregnancy. A single
Structure and Histology of the Umbilical Cord
Figure 6.10. Cross section of mature umbilical cord, near its placental insertion
showing a sparsely cellular Wharton’s jelly, an umbilical vein and two arteries. H&E. ¥20.
umbilical artery, which may be associated with multiple fetal malformations, is present in approximately 1% of cases (see Chapter 15). Rarer
anomalies include local fusion of the two arteries and persistence of the
second (right) umbilical vein, the latter also being associated with malformed fetuses. The mean intravital diameter of the arteries is around
3 mm, and the venous diameter is around twice this size.
Human umbilical vessels differ from the major vessels of similar
caliber in the body in the following ways. Transudation of fluid occurs
in these vessels and this contributes to the formation of amniotic fluid.
The muscular coat of the arteries consists of crossing spiraled fibers. The
venous muscular coats are thinner than those of the arteries and are composed
of separate layers of longitudinal or circular fibers. Each umbilical vessel is
surrounded by crossing bundles of spiraled collagen fibers that form a
kind of adventitia. The endothelial cells are unusually rich in organelles and
thus structurally different from the endothelium of the villous vessels.
Endothelial extensions interdigitate with adjacent muscle cells to form
an endotheliomuscular system. The arteries possess no internal elastic
membrane and have much less elastica than in other similar caliber
arteries. The vein, on the other hand, has an elastic subintimal layer
(Figure 6.11). The umbilical vessels also lack vasa vasorum, except for the
intraabdominal portions in fetuses beyond 20 weeks of gestation. In
general, no nerves traverse the umbilical cord from fetus to placenta and the
placenta has no neural supply.
After delivery, umbilical cords show irregular constrictions of
the arteries, but the mechanism is not clear. It is known that increased transmural pressures exerted on the umbilical arteries led to
vasoconstriction. In addition, many substances induce vasodilatation
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Figure 6.11. Umbilical cord sections of one umbilical artery (right) and a vein
(left). In these sections, one may observe the presence of a delicate subendothelial elastica only in the vein at left. von Gieson ¥160.
or vasoconstriction of the umbilical vessels. Vasodilators include
serotonin, angiotensin, oxytocin, prostaglandins, nitrous oxide, and
atrial natriuretic peptide. Vasoconstrictors include angiotensin II,
5-hydroxytryptamine (5-HT), thromboxane, neuropeptide Y, and
endothelin-1. The functions of these vasoconstrictors are still under discussion, and they may function as mediators of closure of the placental circulation at birth.
Selected References
PHP4, Chapter 6, pages 50–115.
Bourne G. The microscopic anatomy of the human amnion and chorion. Am J
Obstet Gynecol 1960;79:1070–1073.
Bourne G. The human amnion and chorion. London: Lloyd-Luke, 1962.
Bourne GL, Lacy D. Ultrastructure of human amnion and its possible relation
to the circulation of amniotic fluid. Nature (Lond) 1960;168:952–954.
Boyd JD, Hamilton WJ. Electron microscopic observations on the cytotrophoblast contribution to the syncytium in the human placenta. J Anat 1966;
100:535–548.
Cantle SJ, Kaufmann P, Luckhardt M, et al. Interpretation of syncytial sprouts
and bridges in the human placenta. Placenta 1987;8:221–234.
Castellucci M, Zaccheo D. The Hofbauer cells of the human placenta:
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