Download Microscopic Anatomy

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Comparative Anatomy and Histology
60
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20
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Progesterone
10
Estradiol
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5
20
Diestrus
Proestrus
Estrus
Metestrus
Diestrus
FIGURE 17 Mouse estrus cycle. Morphologic changes in the vaginal mucosa associated with hormonal changes during the
mouse estrus cycle. Endometrial morphology also varies with cycle, although not as dramatically as in the human (see Figures
13 and 14). Source: © Elsevier, Inc., www.netterimages.com.
clitoral glands are located anterolaterally in the
subcutaneous tissue, each with a single duct that
opens into the lateral walls of the clitoral fossa.
The 6- to 7.5-cm human vagina is also muscular
and extends from the cervix to the vulva. However,
there are a series of grossly apparent ridges
produced by folding of the wall of the outer third
of the vagina termed rugae. These rugae allow
significant extension and stretching during sexual
intercourse and parturition. The vaginal introitus
opens into the vestibule of the vulva (Figure 2).
The vulva is composed of the mons pubis
anteriorly, which separates into two folds of hairbearing skin termed the labia majora. Medial to
the labia majora are the labia minora, two folds of
tissue covered by squamous mucosa that form the
anterolateral borders to the vestibule of the vulva.
The vestibule contains the clitoris, the urethral
opening, and the vaginal introitus. The clitoris is
located in the anterior portion of the vestibule,
where the labia minora meet. The urethral
opening is immediately posterior to the clitoris
and anterior to the vaginal introitus. Posterior to
the vagina is the perineum, the area between the
vagina and the anus.
Microscopic Anatomy
The vaginal vault in the mouse is lined by a
keratinized stratified squamous epithelium that
undergoes measurable changes during the mouse
estrus cycle (Figures 17 and 18). The mucosa
is folded with no glands. The lamina propria
is composed of connective tissue with circular
and longitudinal muscularis layers, whereas the
outermost layer is formed by adventitia that is
continuous with the rectal and urethral adventitia
(Figure 19). The human vagina is lined by a
nonkeratinized squamous epithelium and does
not undergo the significant morphologic changes
seen in the mouse during the menstrual cycle
(Figure 20). Small changes in the amount of
glycogen accumulation and nuclear maturation
do occur but are minor compared with the
changes seen in the mouse. The outer aspects
of the labia majora are lined by hear-bearing
skin, whereas the inner portions of the labia
majora, the labia minor, and the vestibule are
lined by nonkeratinized squamous mucosa.
The clitoris of the mouse is covered by skin
and hair, whereas that of the human is covered
C h a p t e r 1 7 Female Reproductive System
FIGURE 18 Mouse vaginal epithelial changes during the estrus
cycle. Vaginal mucosa morphology, particularly the numbers of layers
and differentiation, changes during the estrus cycle. Histologically,
four stages of the estrus cycle are easily determined: proestrus, estrus,
metestrus, and diestrus. (A) During proestrus, the mucosa is 10–13
cells thick and the outer layers stain lightly with eosin, whereas
the granulosa layer shows increasing cornification. Mitoses are
frequent, but few leukocytes are present. (B) In estrus, the mucosa is
approximately 12 cells thick. The superficial nucleated layer is lost, and
the cornified layer is superficial. Mitoses are decreasing, and leukocytes
are absent. (C) In metestrus, the cornified layer is delaminated, and
leukocytes begin to appear under the epithelium. (D) During diestrus,
the mucosa is 4–7 cells thick . Surface epithelial cells are mucified, and
mucus, leukocytes, and desquamated cells are present in the lumen.
by squamous mucosa. In mice, paired clitoral
glands are sebaceous glands that empty into the
clitoral fossa via excretory ducts lined by stratified
squamous epithelium (Figure 21). Also opening
into the clitoral fossa is the urethra, which is lined
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l Need-to-know
Mouse vaginal mucosa changes morphology
at each phase of the estrus cycle, whereas
human vaginal mucosa is relatively stable in
morphologic appearance.
n
by transitional epithelium. In humans, there
are periurethral (Skene’s) glands and major
(Bartholin’s) and minor vestibular glands, which
open into the vestibule. Skene’s glands are lined
with pseudostratified, mucus-secreting columnar
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Comparative Anatomy and Histology
CF
CF
VM
B
LP
E
M
U
E
A
FIGURE 19 Mouse vaginal mucosa. The mouse vaginal
mucosa (VM) is composed of stratified squamous epithelium
and is folded into longitudinal elevations with no glands. The
morphology of the vaginal epithelium changes during the
different stages of the estrus cycle. The lamina propria (LP)
is fibrous, and the muscularis (M) layer is thin admixed with
significant fibrous connective tissue. Adventitia (A) makes up
the outermost layer.
(A)
F
PC
CC
CC
S
VM
FIGURE 20 Human vaginal mucosa. The human vaginal
mucosa (VM) is composed of stratified squamous epithelium
with no glands. Unlike that of the mouse, the human vagina
is not keratinized, and the morphology of the human vaginal
mucosa does not change significantly during the menstrual
cycle.
(B)
FIGURE 21 The mouse and human clitoris. (A) The mouse
clitoris is a ventrally extending elevation located on the
anterior wall of the vaginal opening. The tip of the clitoris is
covered by vaginal epithelium, and the anterior lateral surfaces
are covered by haired skin. The urethra (U) opens near the tip
of the clitoris. Erectile tissue (E) similar to penile erectile tissue
surrounds the urethra near the tip of the clitoris. A small bone
(B) homologous with the os penis is surrounded by connective
tissue on the anterior face. The paired clitoral gland
ducts (asterisks)open laterally at the clitoral fossa (CF). (B)
Micrograph of human clitoris. Note the two corpora cavernosa
(CC), arranged side-by-side and engorged with blood, the
incomplete central septum (S), and the fibrocollagenous
sheath (F), outside which are prominent nerve endings
(mainly Pacinian touch corpuscles (PC)). Source: Reprinted
from Human Histology, 3e, Stevens, A., Lowe, J.S., 2004, with
permission from Mosby, © Elsevier. www.netterimages.com
C h a p t e r 1 7 Female Reproductive System
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cells that empty via bilateral periurethral ducts
that are lined by transitional-type epithelium.
Bartholin’s glands are lined by mucus-secreting
columnar cells and empty via bilateral ducts
adjacent to the vaginal introitus that are also lined
by transitional epithelium.
U
(A)
The urethra is lined by transitional epithelium
that merges with the nonkeratinized squamous
epithelium at the urethral orifice. Erectile tissue
surrounds the urethra near the tip of the clitoris
in mice; similar erectile tissue surrounds the
clitoris in humans. The clitoral erectile tissue is
composed of a fine vascular network similar to
that present in the male penis (Figures 21 and 22).
Mice have a small bone in the clitoral connective
tissue, homologous to the os penis; humans do
not have such a structure (Figure 22). The lamina
propria of the clitoris and urethra consists of
connective tissue that blends into the adjacent
connective tissue and dermis.
Placenta
The placenta is the most morphologically diverse
organ across mammalian species (Figures 23–31).
Theories to explain this diversification over
evolutionary history include maternal–fetal
genetic conflict over nutrient allocation.
U
(B)
FIGURE 22 Mouse erectile tissue. Clitoral erectile tissue
(asterisks), similar to penile erectile tissue, surrounds the
urethra (U) near the tip of the clitoris. (A) A small bone
(arrow) homologous with the os penis is surrounded
by connective tissue on the anterior face. (B) Higher
magnification view of vascular erectile tissue.
l Need-to-know
The mouse clitoris is covered by haired skin on the
anterior and lateral surfaces.
n
The mouse clitoris has a small bone homologous to the
os penis.
n
Gross Anatomy
In mice, the placenta is discoid and approximately
2  0.6 cm. The uteroplacental circulation is
similar to that of humans, although the maternal–
fetal interdigitation is labyrinthine rather than
villous (Figure 23 and Table 4).
In humans, the placenta is a disc approximately
20 cm in diameter that has a fetal surface and a
maternal surface that is attached to the uterus
(Figure 24). Maternal blood enters the intervillous
space through the spiral arteries, which have been
modified by invasive fetal trophoblast cells and
transformed into low-resistance vessels. Maternal
blood exits the intervillous space through uterine
veins. Fetal blood enters the placenta through the
umbilical artery, which branches over the fetal
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Comparative Anatomy and Histology
E
DC
E
M
YS
L CP
T
M
DB
E
FIGURE 23 Subgross of mouse gravid uterus. The embryo (E) is contained within the yolk sac (YS). The placental
layers are partially visible at this low magnification and include the chorionic plate (CP), trophoblast (T) that includes
spongiotrophoblasts and giant cells, labyrinth (L), decidua basalis (DB), and capsularis (DC). Myometrium (M) and portions
of additional embryos (E) are indicated.
C h a p t e r 1 7 Female Reproductive System
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YS
YS
CP
L
S
G
MV
MV
D
l Need-to-know
(A)
Mice and humans share hemochorial
placentation.
n
L
S
G
(B)
FIGURE 24 Mouse placenta. (A) Humans and mice share hemochorial placentation. In mice, this organ is fully functional
at embryonic day 12.5, which is equivalent to month 5.6 in humans. In hemochorial placentas, maternal blood comes in
direct contact with fetal membranes through a labyrinth layer (L). Embryonic-derived layers include the labyrinth, the
spongiotrophoblasts (S), and the giant cell trophoblasts (G). The decidual (D) layer is completely derived from maternal
tissue. (B) Embryonal components of the placenta, the labyrinth layer (L), the spongiotrophoblast layer (S), and the giant cell
trophoblast layer (G). CP, allantochorionic plate; MV, maternal vessels; YS, yolk sac.
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Comparative Anatomy and Histology
surface of the placenta, and further branches
enter the chorionic villi containing capillary trees,
with the blood returning in a venous path to the
umbilical vein.
The yolk sac is an extraembryonic membrane that
surrounds the developing embryo. The yolk sac is
derived from embryonic endoderm and mesoderm,
and it provides the primitive circulatory system
and erythropoiesis prior to placenta development.
In the mouse, the yolk sac plays a minor role
in embryonic support following placental
development (Figure 25). In humans, the chorionic
vessels are entirely derived from the allantois, and
the yolk sac does not contribute to maternal–fetal
exchange and is present only as a small remnant at
delivery. It is lined by a single endodermal layer of
tall columnar cells on a thin basal lamina separating
endodermal epithelium from the mesoderm
that gives rise to the blood islands. Blood islands
lined by elongated endothelial-like cells contain
embryonic nucleated erythrocytes (Figure 25). The
yolk sac maintains communication with the embryo
via intralabyrinth sinuses and the margins of the
chorioallantoic plate.
In both mice and humans, the chorioallantoic
plate is formed by the fusion of the allantois and
the chorionic plate (Figures 23 and 26). This
fusion initiates the formation of the placenta. In
mice, the chorioallantoic plate is composed of
umbilical vessels and loosely arranged spindle cells
originating from the extraembryonal ectoderm
(Figure 23).
Both humans and mice have hemochorial
placentas, where the fetal trophoblast is directly
exposed to maternal blood. The hemochorial
placenta is fully developed in the mouse by day 12
of the 18.5- to 21-day gestation period. In humans,
the hemochorial placenta is fully developed by
week 5 of the 37- to 42-week gestation period
(Table 4).
Microscopic Anatomy
In the mouse, layers of placenta include
the chorioallantoic plate, labyrinth layer,
Reichert’s membrane, giant cell trophoblasts,
spongiotrophoblasts, and the decidua (Figure 23).
The embryonal components include Reichert’s
membrane, spongiotrophoblasts, giant
cell trophoblasts, the labyrinth layer, and
chorioallantoic plate. Layers of the human
placenta include the amnion, chorionic plate,
intervillous space, basal plate, and deciduas
(Figure 24). The decidua is the only completely
maternal component in both species. In mice,
the decidua is divided into the basalis and the
capsularis. The heavily vascularized basalis is
located on the mesometrial side, where it interacts
with the spongiotrophoblasts, whereas capsularis
on the antimesometrial aspect is thinner and
less well vascularized. Likewise, in humans, the
decidua at the implantation site, which later
underlies the placenta, is known as the decidua
basalis. The human decidua is further divided into
the decidua capsularis, which covers the surface
of the gestational sac, and the decidua parietalis,
which comprises the decidua on the opposite
uterine wall.
C h a p t e r 1 7 Female Reproductive System
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Placenta I — Form and Structure
Cotyledons
Connective tissue septa
Full-term placenta
Maternal aspect
Fetal aspect
A
C
F
B
D
E
G
B
A
H
FIGURE 25 Human placenta showing the maternal and fetal surfaces as well as the insertion of the umbilical cord. Fetal villi
project into the lacuna system, which is filled with maternal blood. Gas exchange occurs across the syncytiotrophoblast and the
endothelial lining of the fetal vessel within the villous. (Bottom left) Section through deep portion of placenta, early gestation.
A, villus; B, trophoblast; C, intervillous space; D, anchoring villus; E, villus invading blood vessel; F, fibrinoid degeneration;
G, decidua basalis; H, gland. (Bottom right) Appearance of placental villi at term. A, syncytial cell mass becoming trophoblastic
embolus; B, fetal blood vessel endothelium against a thinned syncytiotrophoblast, where they share a basal lamina. The
cytotrophoblast has disappeared. Source: © Elsevier, Inc., www.netterimages.com.
In mice, Reichert’s membrane (Figure 25), a thick
acellular basement membrane that divides the
trophoblast giant cells and the yolk sac, is unique
to the rodent placenta. The mouse labyrinth layer
is a highly vascularized structure composed of
labyrinth trophoblasts; embryonal endothelium,
which forms blood vessels; and embryonal
erythrocytes (Figure 27). Maternal blood cells
fill spaces lined by labyrinth trophoblasts. It is
not uncommon to see mineralization in the
labyrinth layer as a normal finding (Figure 28).
The spongiotrophoblast layer is composed of large
cells with abundant, often vacuolated, eosinophilic
cytoplasm (Figure 29). This layer forms just
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Comparative Anatomy and Histology
BI
BI
BI
l Need-to-know
(A)
Beyond embryonic day 12.5, when the placenta is fully
developed, the yolk sac plays a minor role in embryonic
support.
n
YS
Reichert’s membrane is unique to rodents.
n
T
(B)
FIGURE 26 Mouse placenta. (A) Yolk sac from day 16.5 of gestation. The parietal and visceral layers of the yolk sac are lined
by tall columnar cells. A thin basal lamina separates the epithelium from the mesoderm and blood islands (BI), which are lined
by endothelial-like cells and contain immature and mature erythrocytes. (B) Reichert’s membrane is unique to the rodent
placenta. Reichert’s membrane (asterisk) forms an acellular basement membrane that separates the trophoblasts (T) and the
yolk sac (YS).
below the labyrinth and is traversed by maternal
vessels. Spongiotrophoblasts may phagocytize
maternal erythrocytes or have pink hyaline
cytoplasmic globules (Figure 29). The globules
may dramatically increase with trophoblast
degeneration. Between the spongiotrophoblasts
and the maternal decidua is the giant cell
trophoblast layer. These cells have abundant
eosinophilic cytoplasm and large nuclei. Giant cell
trophoblasts are frequently greater than 100 μm
in diameter, and individual nuclei can be greater
than 50 μm in diameter (Figure 30). The decidua
makes up the maternal portion of the placenta
(Figure 30). Cells are haphazardly arranged and
typically have diffuse cytoplasmic vacuolation and
irregularly shaped nuclei. Large maternal vessels
develop to support the pregnancy. At Reichert’s
membrane, giant cell trophoblasts extend into the
C h a p t e r 1 7 Female Reproductive System
AE
AM
FV
CM
IVS
FIGURE 27 Human placenta. The human chorionic plate. The plate is lined by amniotic epithelium (AE), amniotic
mesoderm (AM), and chorionic mesoderm (CM). FV, fetal vessel; IVS, intervillous space.
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Comparative Anatomy and Histology
SK
V
M
IVS
M
V
V
V
SK
(A)
FIGURE 28 Mouse and human placenta. (A) The labyrinth
layer is highly vascularized with embryonic and maternal blood.
The embryonic blood channels (V) are lined by embryonic
endothelial cells and contain immature erythrocytes. Labyrinth
trophoblasts line vascular channels filled by maternal blood (M).
Mineral (asterisk) is not uncommon in normal animals. (B) The
human intervillous space (IVS) is perfused by maternal blood.
Highly vascularized fetal villi are lined by villous trophoblast
(arrow). SK, syncytial knot; V, fetal vessel. Source: Courtesy of
T. B. Treuting.
decidua to form a sinusoidal network, the vitelline
meshwork. This meshwork is filled with maternal
blood.
In humans, the chorion laeve or fetal membranes
are formed at the edge of the placental disc by
fusion of the basal plate and chorionic plate by
obliteration of the intervillous space (Figure 26).
The fetal surface is lined by amniotic epithelium
composed of a single layer of cuboidal to
columnar cells, an unkeratinized stratified
squamous epithelium over the umbilical cord.
(B)
l Need-to-know
Mineralization is commonly observed in the
labyrinth and trophoblast layers in normal
pregnancies.
n
Connective tissue subjacent to the amnion
contains fetal vessels and residual trophoblast.
Subjacent to the chorion laeve is the maternally
derived decidua capsularis, which is derived from
decidualized maternal endometrium.
There are two major populations of human
trophoblast. The first population is the villous
trophoblast that lines the chorionic villi, the
site of maternal–fetal exchange (Figures 24,
27, and 28), and is composed of two layers.
The outmost layer, the syncytiotrophoblast, is