Female Reproductive System
The internal sex organs of the female include the ovaries, oviducts,
uterus and vagina. We will not be looking at the histology of the external
genitalia.
The gametes (ova) and sex hormones of the female are produced by the ovaries. Each
ovary has a cortex and a medulla. The outer part, the cortex, has a stroma of dense, very
cellular, connective tissue whose fibres run in various directions and give it a swirly
appearance. Primary oocytes and their surrounding follicular cells, which together are
referred to as a follicle, are embedded in the cortex. The sex cells are all primary
oocytes because all the oogonia differentiate to primary oocytes before birth. The sex
cell remains a primary oocyte throughout the stages of growth of the follicle. The primary
oocyte completes its first meiotic division just before ovulation, and the ensuing
secondary oocyte begins the second meiotic division but stops at metaphase. The second
meiotic division is completed only upon fertilization. The more immature follicles
(primordial follicles) are found toward the periphery of the cortex, as they grow they
move inward. The inner part of the ovary, the medulla, is continuous with the mesovarium
that attaches the ovary to the broad ligament of the uterus. The
medulla is made of loose fibroelastic connective tissue. Blood vessels, lymph vessels and
nerves enter through the medulla.
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 Low power view of the cortex of the ovary 
Figure 1 shows a low power view of the cortex of the ovary. The outer part of the
cortex is lined by a cuboidal epithelium (not identifiable as such at this magnification),
erroneously given the name germinal epithelium, which unfortunately has stuck. (The
epithelium is not involved in producing the germ cells or gametes and is therefore not
germinal). Underneath the epithelium is a layer of dense connective tissue called the
tunica albiguinea. In the more pink-staining stroma of the cortex many follicles can be
seen. Most of the follicles seen here are primordial follicles (discussed below). The
nucleus of the oocyte can be seen in many of the primordial follicles. |
High power view of early follicles in the cortex of the
ovary
Figure 2 shows a higher magnification view of early follicles embedded in the stroma of
the cortex. The earliest follicles are called primordial follicles. A primordial follicle
consists of a (primary) oocyte and a single layer of squamous follicular cells surrounding
it. All the follicles that a baby girl is born with are primordial follicles, none start
to develop until puberty. With each menstrual cycle, some (up to about 20) primordial
follicles begin to grow. Only one generally makes it to a mature (Graafian) follicle which
will be ovulated, the rest undergo atresia (die).
The first step in follicular growth involves the squamous follicle cells becoming
cuboidal. When that happens, the follicle is called a primary follicle. A primary follicle
with cuboidal cells is seen in the lower right of Figure 2. (Note that the term primary
follicle does not refer to stage of the oocyte – which, as discussed above, is a
primary oocyte throughout all the stages of follicular development). When the follicle is
surrounded by a single layer of cuboidal cells it is called a unilaminar primary follicle;
when more cell layers are added, it is a multilaminar primary follicle. In some of the
follicles of Figure 2, the section did not pass through the oocyte itself but only the
follicular cells, these are indicated by asterisks. |
 High power view of
primary follicle
Figure 3 shows a high power view of some primary follicles, a number of which are
becoming multilaminar. The nuclei of some follicles can be seen. |
 High power view of multilaminar primary follicle
Figure 4 shows a high power view of a multilaminar primary follicle. The nucleus is
clearly seen in this section. A prominent zona pellucida is present. As the follicle cells
around the oocyte become statified, they are referred to as granulosa cells, and the
epithelium as a whole is called the stratum granulosum. The inner layer of granulosa cells
appears to have already arranged itself into a corona radiata: a radially-arranged layer
of columnar cells that surrounds the oocyte and is generally more evident in secondary and
Graafian follicles (described below). The stroma surrounding the oocyte is beginning to
become organized into a theca. Some of the cells of the theca interna will become more
cuboidal and secretory (they will be involved in steroid production, along with the
granulosa cells). The theca externa does not differ markedly from the surrounding stroma
(consisting of connective tissue cells, collagen fibres, and some smooth muscle cells),
but tends to be more organized.
As the primary follicle grows, cavities begin to appear among the granulosa cells. When
this happens, the follicle is called a secondary follicle. The fluid-filled cavities
become larger and eventually begin to fuse. When the cavities have all fused to form a
single large cavity, the latter is called the antrum. The oocyte gets pushed from a
central position to the periphery. Some granulosa cells still cover the part of the oocyte
that projects into the antrum. These cells, and the cells that the oocyte sits on, are
called the cumulus oophorus. The innermost layer of columnar cells that surrounds the
oocyte (separated only by the zona pellucida) is called the corona radiata. (Therefore the
corona radiata is part of the cumulus oophorus). When the follicle is mature (large
antrum), it is called a Graffian follicle. |
Secondary follicle with cavities
Figure 5 shows a secondary follicle with two large cavities. Unfortunately, the oocyte
itself is not in very good shape, and a zona pellucida and corona radiata are not
identifiable. However, the cumulus oophorus surrounding the oocyte can be identified. The
theca interna is distinguishable from the surrounding stroma. The fuzziness inside the
cavities is due to the staining of the follicular fluid. A primary follicle is visible to
the lower left. The structure to the right of that follicle appears to be another primary
follicle, undergoing atresia. A number of primordial follicles are visible below (which is
toward the periphery of the cortex). |
 Low power view of
Graafian follicles
Figure 6 shows a low magnification view of two Graafian follicles. Only the one on the
right was sectioned through the oocyte (again, not in the best shape). Notice the large
size of the Graafian follicles compared with the primordial follicles lying between them
and the tunica albiguinea. The oocyte itself has also increased in size, but not to the
same extent as the follicle as a whole. Notice how the more mature follicles move
centrally (toward the medulla) and the earlier follicles are at the periphery of the
cortex. |
Follicles undergoing atresia
Since only one (or a few) of all the follicles that begin to develop during any
menstrual cycle make it to maturity, many follicles undergo atresia. A follicle can
undergo atresia during any stage of development. Figure 7 shows two atretic follicles.
Note the disorganization of the follicular cells, and the degeneration of the oocyte. In
the lower follicle, only the zona pellucida is still present, it looks like a rubber band.
(The zona pellucida is often the most persistent part of an atretic follicle.)
After ovulation, the collapsed follicle undergoes reorganization. The walls of the
remaining granulosa cells and theca interna cells are thrown into deep folds. A temporary
corpus hemorrhagicum with a central blood clot is formed due to bleeding of the
capillaries of the theca interna. The former cavity is invaded by and replaced with
connective tissue, and the granulosa and theca interna cells undergo morphological
changes. They increase in size and become filled with lipid droplets. The cells are now
called, respectively, granulosa lutein cells and theca lutein cells. Both cell types
hypertrophy, with the granulosa lutein cells becoming much larger than the theca lutein
cells. Granulosa lutein cells constitute most of the corpus luteum. Theca lutein cells
stain more deeply and are located peripherally or along the folds of the corpus luteum.
The cells of the corpus luteum produce progesterone and estrogen. A rich vascular network
to transport these hormones arises from vessels of the (former) theca interna, which grow
into the (former) granulosa cells as these are reorganizing to become the corpus luteum.
In the absence of fertilization, the corpus luteum lasts for 10 days to two weeks. In the
event of pregnancy, the corpus luteum persists for the duration of the pregnancy and can
become very large. |
 Low power view of a
corpus luteum
Figure 8 shows a low magnification view of the corpus luteum from a pregnant sow. The
boundaries are shown by asterisks. Some primordial follicles are visible below it. Note
the relative sizes. (Corpora lutea can also be smaller than the one shown here). |
High power view of corpus luteum
Figure 9 shows a high power view of the corpus luteum. Most of the cells are the
large, vacuolated granulosa lutein cells. Theca lutein cells are not as large therefore
their nuclei appear closer together. Blood vessels can be seen among the cells. A rich
vascular supply is essential for endocrine organs.
The corpus luteum, whether of menstruation or pregnancy, will eventually degenerate by
autolysis and its cells phagocytised. The site of the corpus luteum will be replaced by
dense connective tissue, which is called corpus albicans. The corpus albicans is
eventually resorbed by macrophages and replaced by stroma. |
 Low
power view of a corpus albicans
Figure 10 shows a large corpus albicans from a menopausal ovary. Note that you cannot
see any follicles in the stroma.
Menstrual cycles decrease in frequency between the ages of 45 and 55 and eventually
cease (menopause). In the menopausal ovary, the remaining follicles degenerate and are
replaced by stroma. |
Cortex of menopausal ovary
Figure 11 shows the stroma of a menopausal ovary. Note that there are no follicles of
any type present. Corpora albicantia can still be in evidence in menopausal ovaries (not
seen in this figure). |
 Low power view of ovarian
medulla
Figure 12 shows the medulla of an ovary, with blood and lymph vessels. Nerve bundles
cannot be identified at this magnification. Note part of the antrums of three Graafian
follicles can be seen below (toward the cortex). |
Low power view of oviduct
Upon ovulation, the egg enters the oviduct. The wall of the oviduct has 3 layers: a
mucosa (epithelium plus lamina propria), a muscularis and a serosa. A distinguishing
feature of the mucosa is its many tall and branching folds. These are evident in the low
power view of the oviduct in Figure 13. A serosa is not easily distinguished in this
figure. Fertilization and development up to the morula stage occurs in the oviduct. |
High power view of mucosa of oviduct
 Figure
14 shows a higher power view of the mucosa of the oviduct. There are two types of cells in
the simple columnar epithelium, ciliated cells and non-ciliated secretory cells called peg
cells. Peg cells are distinguished by lack of cilia and the fact that they sometimes
appear to stick out over the ciliated cells they lie between. When the section is more
than one cell layer thick, it is difficult to be sure that a particular cell lacks cilia.
(Thus peg cells can be difficult to find). The lamina propria is very cellular and
well-vascularized.
The bulk of embryonic and fetal development occurs in the uterus. The uterus has three
layers. Its innermost layer or mucosa, is called the endometrium. The middle muscular
layer (muscularis) is called the myometrium, and consists of three (poorly defined) smooth
muscle layers. Its serosa is called the perimetrium.
The endometrium consists of an epithelium and underlying lamina propria. The epithelium
is simple columnar with secretory and some ciliated cells. The lamina propria is higly
cellular.
Two layers constitute the endometrium. One layer, the stratum basalis, does not undergo
major changes during the menstrual cycle and is not sloughed off. The other layer, the
stratum functionalis, undergoes dramatic changes during the menstrual cycle. It builds up
during the follicular (proliferative, estrogenic) phase under the influence of estrogens.
It becomes maximal after ovulation under the influence of progesterone from the corpus
luteum. It is sloughed off during the menstrual phase. Straight tubular glands extend from
the stratum basalis, through the stratum functionalis to the lumen of the uterus. The
epithelium of the glands is continuous with that of the surface epithelium. During
menstruation, only the bases of the glands (in the strtum basallis) remain.
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Low power view of uterine endometrium during follicular
phase
Figure 15 shows the endometrium during the follicular phase. A line shows the
approximate border between the basalis and functionalis. Note that the glands are straight
and narrow and much stroma lies between glands. |
 High power view of endometrium, follicular phase
Figure 16 shows a higher power view of the endometrium in the follicular phase with
glands, cut in longitudinal section, emptying into the lumen. Other glands, cut incross
section, appear as circular profiless. |
High magnification of gland opening into lumen at
endometrial surface
Figure 17 shows a high power magnification of the surface epithelium opening into a
gland. The simple columnar epithelium continues into the glands. Note two profiles of
blood vessels in the cellular lamina propria. |
High magnification of spiral artery in endometrium in
proliferative stage
Figure 18 shows four profiles of a spiral artery lying between some uterine glands. The
smooth muscle making up the tunica media of the artery is distinguishible from the simple
columnar epithelium of the glands. Bulging endothelial cells can be seen in most of the
arterial profiles.
During the secretory (or luteal or progesterone) phase, the glands in the endometrium
increase in number and size, eventually occupying most of the endometrium, with little
stroma between them. They become sacculated and filled with secretory product, rich in
glycogen and glycoproteins. |
Low magnification of endometrium in the secretory phase
Figure 19 shows the endometrium of the uterus in the secretory phaseA line demarkates
the apporximate border between the stratum basalis and the stratum functionalis. The
entire endometrium is not shown, it continues to the left. . A bit of the myometrium is
visible to the right. Many lymphocytes are present near the basalis (not visible at this
magnification). |
 Low power view of
cervical glands
Figure 20 shows a low power view of the cervix. The cervix has numerous
branching, mucous-secreting glands called cervical glands. The cervix lacks spiral
arteries and does not change in thickness or become sloughed off during the menstrual
cycle. However the abundance and nature of the mucous changes in accordance with the
cycle. Near the time of ovulation the mucous increases by about a factor of 10 over that
at the beginning of the cycle, and this mucous is favorable to sperm movement, whereas
earlier mucous is restrictive.
The cervical glands have simple columnar epithelium, which is continuous with the
surface epithelium. Mucous is often evident as pink-staining material along the surface.
The lamina propria is also very cellular. The muscle wall is continuous with that of the
body of the uterus, but not as extensive. Some smooth muscle fibres of the muscularis are
visible at the bottom of Figure 20. |
Simple columnar epithelium of cervix
Figure 21 shows a high power view of the simple columnar epithelium of the cervical
glands which is continuous with that of the surface. |
 Transition
of cervical to vaginal epithelium at external os
Figure 22 shows a low magnification view of the external os of the cervix where the
simple columnar epithelium (with glands) of the cervix changes abruptly to the stratified
squamous epithelium of the vagina. Note the vascularized lamina propria. The muscularis is
also visible. |
Low power view of the vagina
Figure 23 shows a low power view of the vagina, which consists of an epithelium, a
lamina propria and a muscularis. Notice the many blood vessels of the lamina propria,
which is composed of moderately dense connective tissue with many elastic fibres (not
visible without special stains). The vagina does not have glands and is lubricated by the
secretions of the cervical glands and exudates from the many blood vessels in the lamina
propria. These blood vessels also make the vagina a quasi-erectilve tissue during sexual
stimulation. Blood vessels, with much thicker walls, are also seen in the muscularis. |
 Vaginal mucosa
Figure 24 shows a high power view of the epithelium and lamina propria of the vagina.
The stratified squamous epithelium is non-keratinizing. During the follicular (or
proliferative) phase, estrogens cause the epithelial cells to synthesize and accumulate
glycogen as they migrate to the surface. Glycogen released into the lumen is metabolized
by bacteria to produce lactic acid, rendering the vagina acidic. Epithelial cells are
continuously desquamated; during menstruation the whole superficial layer may be shed.
The lamina propria has many blood vessels. Many lymphocytes are also present,
especially near the epithelium. (They are a bit hard to see at this magnification, the
asterisk shows where they are abundant, as little dots). Many lymphocytes migrate into the
epithelium. The number of lymphocytes increases greatly during menstruation. |
Development & Homeostasis| Immunology | Cardiovascular | Respiratory 