H I S T O L O G Y
L E C T U R E
MALE REPRODUCTIVE SYSTEM
OBJECTIVES:
Upon completion of the study of this section the student will be able to:

List the exocrine functions of the testes.

Describe the three stages of spermatogenesis and expand upon the phases of
spermiogenesis.

Discuss the four functional roles of Sertoli cells, include their relationship to the
blood-testes barrier.

Review the endocrine functions of the testes, include the activities of both
sustentacular (sertoli) and interstitial (Leydig) cells.

Trace the path of a sperm from it’s release by the Sertoli cell through it’s
ejaculation.

List and describe the function of the three accessory genital glands.

Contrast the sites of action for FSH and LH.
Male Reproductive System






consists of the testes contained in the scrotum, the genital ducts and their associated
glands (accessory glands) and the penis.
testes function to produce spermatozoa (sperm) and to synthesize the hormone
testosterone.
major accessory glands include the paired seminal vesicles and the single prostate gland.
minor accessory glands include the two bulbourethral glands located at the root of the
penis.
accessory glands function to manufacture the fluid portion of the semen, which transports
and nourishes the spermatozoa as they pass through the excretory ducts.
penis is the male copulatory organ that delivers spermatozoa into the female reproductive
tract and serves as a conduit for excretion of urine from the body.
Testes
Testis

is an ovoid body, about 4 to 5cm long, that is housed within the scrotum.

develops retroperitoneally in the abdominally cavity and descends into the scrotum,
carrying parietal and visceral layers of the peritoneum (the tunica vaginalis) that partially
cover the testis on its anterior and lateral surfaces.
Tunica Albuginea

is the thick fibrous connective tissue capsule of the testis.

is thickened posteriorly to form the mediastinum testis from which connective tissue
septa arise to divide the organ into approximately 250 compartments (lobuli testis).
Lobule Testis

are pyramidal-shaped incomplete compartments that intercommunicate.

contain from 1 to 4 seminiferous tubules each, embedded in a meshwork of loose
connective tissue where nerves, vessels, and scattered interstitial cells of Leydig are
present.
Interstitial Cells of Leydig

are located in the interstitial spaces between the seminiferous tubules.

mature and begin to secrete during puberty and are richly supplied with capillaries and
lymphatic vessels.
are round to polygonal in shape, possessed a large central nucleus, many mitochondria, a
well-developed Golgi apparatus, and many lipid droplets.
are endocrine cells that produce the male sex hormone testosterone, when stimulated by
luteinizing hormone (interstitial cell stimulating hormone) from the pituitary gland.


Seminiferous Tubules

are the sites where spermatozoa are produced.

are 30 to 70 cm long, with a diameter of 150 to 250 um.

are lined by a complex, stratified epithelium.

are enveloped by a fibrous connective tissue tunic, composed of several layers of
fibroblasts. Myoid cells, resembling smooth muscle, are present in the inner layer of
some species, but not in humans.
form tortuous pathways through the organ before they become continuous with the short
straight tubuli recti.

Tubuli Recti

have a narrow lumen lined by a simple cuboidal epithelium.

lead into the rete testis, a network of epithelial-lined channels located in the mediastinum.
Ductuli Efferentes

lead from the rete testis into the epididymis.
Seminiferous Epithelium


is composed of two different types of cells, the spermatogenic cells from which the germ
cells eventually develop and the Sertoli cells, which support and provide nutrition to the
spermatogenic cells.
is 4 to 8 cell layers thick.
Sertoli Cells






are columnar, extremely complex in shape, and extend from the basal lamina to the
lumen.
their apical and lateral plasma membranes are markedly irregular in outline since they
envelope the developing germ cells.
contain a well-developed smooth endoplasmic reticulum, some rough endoplasmic
reticulum, an abundance of mitochondria and lysosomes, and an extensive Golgi
apparatus.
nucleus is pale, oval, displaying frequent indentations and a large nucleolus.
form occluding junctions with adjoining Sertoli cells, thus subdividing the lumen of the
seminiferous tubule into a basal and an adluminal compartment.
zonulae occludentes are responsible for establishing the blood-testis barrier that serves to
protect the developing sperm cells from autoimmune reactions.
Functions

of Sertoli cells are manifold.

support, protect, and nourish developing spermatozoa.

phagocytose excess cytoplasm discarded by spermatids in the process of spermiogenesis.
secrete a fluid into the seminiferous tubules that transports spermatozoa to the genital
ducts.
contain FSH receptors and under FSH influence synthesize androgen-binding protein
(ABP) that binds testosterone, concentrating it to permit sperm maturation.
secrete inhibin, a hormone that inhibits synthesis and release of FSH from the anterior
pituitary.



Spermatogenic Cells


include several characteristic cell types in the seminiferous epithelium: spermatogonia,
primary spermatocytes, secondary spermatocytes, spermatids, and spermatozoa.
each of these cells represents a distinct stage in the differentiation of male germ cells.
The entire process is known as spermatogenesis.
Spermatogenesis

is divided into three phases: spermatocytogenesis, meiosis, and spermiogenesis.

in man takes approximately 64 days; its cell divisions are unusual, in that the daughter
cells remain connected to each other via intercellular bridges (forming a syncytium).
Syncytium
 may be responsible for the synchronous development of germ cells along any one
seminiferous tubule.

is disrupted at the completion of spermatogenesis, when the individual spermatozoa are
released into the lumen.
Spermatocytogenesis

refers to division of the spermatogonia to provide a continuous supply of cells that will
give rise to primary spermatocytes.
Meiosis
 are two successive divisions that reduce the chromosome number from diploid to haploid
and produce spermatids.
Spermiogenesis

is cytodifferentiation and transformation of spermatids to form spermatozoa.
Spermatogonia
 are the diploid germ cells that sit upon the basal lamina.

are of three types: pale type A, dark type A, and type B.
Pale Type A
 are small (about 12 um diameter) and possess a pale-staining nucleus and cytoplasm
containing spherical mitochondria, a small Golgi complex, and abundant free ribosomes.
 at puberty these cells undergo mitosis and give rise to either more pale type A
spermatogonia (to maintain the supply of spermatogonia) or type B spermatogonia
(which undergo mitosis and give rise to primary spermatocytes).
Dark Type A
 (with dark nuclei) represent noncycling, reserve cells that have the potential to produce
more pale type A cells.
Primary Spermatocytes

are identified as the largest germ cells in the seminiferous epithelium.

are diploid cells (46 chromosomes) that undergo meiosis.
Prophase

of the first meiotic division is long (it takes more than 22 days).

including several stages: leptotene, zygotene, pachytene, diplotene (during which
crossing over, the exchange of genetic material between homologous chromosomes,
occurs) and diakinesis.
is followed by metaphase I, anaphase I, and telophase I, which compose the first meiotic
division.

First Meiotic Division

results in the formation of small secondary spermatocytes.
Secondary Spermatocytes


possess the haploid number of chromosomes (23), and the amount of DNA has been
reduced (from 4N to 2N).
quickly undergo the second division, producing spermatids.
Spermatids

are haploid cells with 23 chromosomes and one-half the amount of DNA (since no S
phase took place).
are small (7 to 8 um diameter) and located near the lumen of the seminiferous tubule.

their nuclei often display regions of condensed chromatin.

contain a pair of centrioles, mitochondria, free ribosomes, smooth endoplasmic reticulum,
and a well-developed Golgi apparatus.
undergo the cytodifferentiation process known as spermiogenesis.


Spermiogenesis



is the unique differentiation process whereby spermatids transform into spermatozoa that
are release into the lumen of the seminiferous tubule.
acrosome and sperm tail are formed during spermiogenesis, the nucleus becomes
condensed and elongated, and excess cytoplasm not directly involved in forming the
spermatozoa is shed and phagocytosed by Sertoli cells.
is divided into four phases: Golgi, cap, acrosome, and maturation phases.
Golgi Phase

of spermiogenesis is characterized by the formation of proacrosomal granules in the
Golgi complex.
Proacrosomal Granules
 coalesce to form a single acrosomal granule enclosed within an acrosomal vesicle, which
becomes attached to the anterior end of the nuclear envelope.
Centrioles

migrate away from the nucleus to form the flagellar axoneme and then retreat toward the
nucleus and assist in forming the connecting piece associated with the tail.
Cap Phase

involves the expansion of the acrosomal vesicle over much of the nucleus, to form the
acrosomal cap.
Acrosomes

contain hydrolytic enzymes (acid phosphatase, neuraminidase, hyaluronidase, protease,
and phosphatase).
Acrosomal Reaction
refers to the release of enzymes that facilitate the dissociation of the cells of the corona
radiata and the digestion of the zona pellucida.

Acrosome Phase
is characterized by the nucleus becoming condensed and flattened, mitochondria
aggregating around the proximal portion of the flagellum to form the middle piece, and
elongation of the spermatid.

Elongation

may be facilitated by a cylinder of microtubules, the manchette. By the end of the
acrosome phase the spermatids are oriented with their acrosomes pointing toward the
base of the seminiferous tubule.
Maturation Phase


is characterized by excess cytoplasm being discarded (including the intercellular bridges
that connected the spermatids) and phagocytosed by Sertoli cells.
is completed when nonmotile spermatozoa are released (tail first) into the lumen of the
seminiferous tubule.
Cycle of Seminiferous Epithelium

refers to the wave-like sequence of maturation that occurs along the seminiferous tubules.
One Cycle

is the reappearance of identical cell associations within the epithelium.

in humans is approximately 16 days, so that four cycles (64 days) must occur for a
spermatogonium to be transformed into a spermatozoon.
Histophysiology
Temperature




of 35oC is critical for the development of spermatozoa.
is achieved in the scrotum by the pampiniform plexus of veins that wrap around the
testicular artery and function to dissipate heat.
is achieved also by evaporation of sweat from the skin of the scrotum.
below 35oC, contraction of the cremaster muscle in the spermatic cord brings the testis
close to the body wall to increase the temperature.
Cryptorchidism

is a condition when the testes fail to descend into the scrotum during development.

the normal body temperature inhibits spermatogenesis, resulting in sterility. However,
this condition does not affect testosterone production.
Luteinizing Hormone (LH)

of the pituitary gland stimulates the interstitial cells of Leydig to secrete testosterone,
which is responsible for the normal development of male germ cells and secondary sex
characteristics.
Follicle-Stimulation Hormone (FSH)

of the pituitary gland acts on the Sertoli cells, promoting the synthesis of androgenbinding protein (ABP).
ABP


binds with testosterone and maintains a high concentration of testosterone in the
seminiferous tubules, where it is essential for spermatogenesis.
binds estrogens and inhibits spermatogenesis. Increased testosterone levels inhibit LH
release, whereas FSH release is stopped by inhibin (secreted by Sertoli cells).
Genital Ducts

convey the spermatozoa and semen to outside of the body.

extend from the seminiferous tubules to the urethra. Although they are continuous, they
are structurally and histologically different. Their names identify the regional division
and unique characteristics they possess.
Tubuli Recti


are short straight tubules, located in the mediastinum testis, which convey spermatozoa
from the seminiferous tubules to the rete testis.
their lumen is lined by a simple cuboidal epithelium having cells that possess microvilli
and a single flagellum on their luminal surface.
Rete Testis


is a labyrinthine plexus of anastomosing channels within the mediastinum testis that
connect the tubuli recti with the ductuli efferentes.
are lined by a simple cuboidal epithelium, and, like those of the tubuli recti, many of the
cells possess a single flagellum.
Ductuli Efferentes

is a collection of 10 to 20 tubules leading from the rete testis to the ductus epididymis.

are lined by a simple epithelium, composed of alternating clusters of (nonaffiliated)
cuboidal and (ciliated) columnar cells.
Cuboidal Cells

possess microvilli, contain lysosomal granules, and function to reabsorb fluid from the
semen.
Ciliated Columnar Cells

aid in transporting the nonmotile spermatozoa toward the epididymis.
Smooth Muscle

in the form of a thin circular layer underlies the basal lamina surrounding the ductuli
efferentes epithelium.
Ductus Epididymis

begins as the terminal portions of the ductuli efferentes fuse.

is a narrow, highly coiled tubule, 4 to 6 meters long.

is surrounded by connective tissue containing blood vessels.

is subdivided into a head, body, and tail region.

its lumen is lined pseudostratified columnar epithelium.
Epithelium

is composed of basal and principal cells.
Basal Cells

are round and appear undifferentiated, apparently serving as precursors of the columnar
principal cells.
Principle Cells

possess stereocilia (long irregular branching microvilli) on their luminal surface.

also possesses endoplasmic reticulum, a large Golgi complex, lysosomes, and many
pinocytotic and coated vesicles in their apical portions (suggesting fluid resorption).
secrete glycerophosphocholine, a substance that probably inhibits capacitation.

Capacitation

is a process whereby the sperm becomes capable of fertilizing the ovum, and, although it
begins in the epididymis, it is not completed until the sperm reaches the oviduct.
Basal Lamina

supports the epithelium and is in turn surrounded by circular layers of smooth muscle,
which increase in thickness and undergo peristaltic contractions that move the sperm
toward the ductus deferens.
Ductus Deferens (vas deferens)

begins at the end of the ductus epididymis as a straight tube with a thick muscular wall.
Pseudostratified Epithelium
 (with stereocilia) similar to that of the ductus epididymis, lines the narrow, irregular
lumen of the ductus deferens.
Muscular Wall

is composed of inner and outer layers of longitudinally oriented smooth muscle,
separated from one another by a middle circular layer.
Ampulla

is the dilated portion of the ductus deferens that leads directly to the prostate gland.
its

epithelium is thickened and greatly folded.
its distal end receives the seminal vesicle, thus forming the ejaculatory duct that enters
the prostate gland.
Ejaculatory Duct


is the straight continuous of the ductus deferens beyond where it receives the ducts of the
seminal vesicles.
lacks a muscular wall. It enters the prostate gland and terminates as a slit on the
colliculus seminalis, in the prostatic urethra.
Accessory Genital Glands

include the seminal vesicles, the prostate gland, and the bulbourethral glands.

produce most of the seminal fluid.
Seminal Vesicles


are the paired tortuous tubular glands (15 cm in length) located adjacent the posterior
aspect of the bladder.
their ducts join the ductus deferens just prior to its entering the prostate gland.
Psuedostratified Columnar Epithelium

lines the extensively folded mucosa of this gland.

consists of low columnar cells interspersed with cuboidal basal cells (whose height is
testosterone dependent).
Columnar Cells

have many yellow lipochrome pigment granules and secretory granules, contain a large
Golgi apparatus, many mitochondria, and an abundant rough endoplasmic reticulum.
Lamina Propria

consists of fibroelastic connective tissue surrounded by an inner circular and an outer
longitudinal layer of smooth muscle.
Adventitia

is also composed of fibroelastic connective tissue.
Secretory Product

is a yellow, viscous fluid that is rich in fructose and other substances and constitutes
about 70% of the human ejaculate.
Prostate Gland

surrounds the urethra as it exits the urinary bladder and is the largest accessory gland.

consist of 30 to 50 discrete branched tubuloalveolar glands that empty their contents into
the prostatic urethra (via excretory ducts).
Glands of the Prostate


are arranged in three concentric layers (mucosal, and main) around the urethra and are
surrounded by a fibroelastic capsule that contains smooth muscle.
stroma from the capsule penetrate the gland and divide it into lobes.
Simple or Pseudostratified Columnar Epithelium

lines the glands, and the fibroelastic connective tissue enveloping them contains elastic
fibers and is richly vascularized.
Epithelial Cells

contain abundant rough endoplasmic reticulum, a well-developed large Golgi
complex, numerous lysosomes, and many secretory granules.
Prostatic Concretions

composed of glycoprotein are sometimes observed in the lumina of the glands.

may become calcified and their numbers increase with age.
Secretion

of the prostate, under the influence of dihydrotestosterone, is a whitish, thin fluid
containing proteolytic enzymes, citric acid, acid phosphatase, and lipids.
Prostatic Carcinoma

induces elevated acid phosphatase blood levels, which is used as diagnostic tool.
Bulbourethral Glands (Cowper’s glands)


located adjacent to the membranous urethra, empty their clear secretion into the lumen to
lubricate it.
are lined by a simple cuboidal or columnar epithelium. Wide fibroelastic septa
(containing smooth and skeletal muscle cells) extend from the capsule to subdivide the
gland into lobules.
Penis

functions both as an excretory organ for urine and as a copulatory organ for delivering
sperm into the female reproductive tract.
is composed of three cylindrical masses of erectile tissue. The paired corpora cavernosa
lie dorsally and the single corpus spongiosum contains the penile (spongy) urethra.
is covered by skin that overlies a loose connective tissue sheath that surrounds the
corpora cavernosa and corpus spongiosum.
skin (distally) lacks hair follicles and contains only a few sweat glands.

hypodermis contains a prominent layer of smooth muscle but no adipose tissue.



Prepuce

that portion of skin that covers the glans penis.

resembles as mucous membrane, since it is lined by stratified squamous nonkeratininzed
epithelium.
Tunica Albuginea

is the thick fibrous connective tissue sheath surrounding the three erectile bodies.

The arrangement of the dense collagen bundles in the tunica permit extensibility of the
penis during erection.
Corpora Cavernosa

are the two-paired erectile bodies dorsally in the penis.

contain irregular vascular spaces lined by a continuous layer of endothelial cells
separated from each other by trabeculae of connective tissue and smooth muscle cells.
Vascular Spaces

are decreased in size toward the periphery of the corpora.

become engorged with blood during erection, making the penis turgid.
Corpus Spongiosum

is the singular erectile body surrounding the spongy urethra.

its erectile tissue is similar to those of the corpora cavernosa, except that the trabeculae
contain more elastic fibers and only a few smooth muscle cells.
its vascular spaces are uniform throughout.

Glands of Littre

are mucus secreting glands that are also present throughout the length of the penile
urethra.
Glans Penis


is the terminal end of the corpus spongiosum.
contains dense connective tissue and longitudinal muscle fibers.
Erection

occurs when the erectile tissues become distended with blood due to parasympathetic
stimulation mediated by tactile or erotic stimulation.
Parasympathetic Impulses

constrict arteriovenous shunts and dilate the helicine arteries, which force blood into the
spaces of the erectile bodies under pressure, engorging them with blood.
Ejaculation

and/or termination of erotic stimulation causes diminished parasympathetic activity,
followed by detumescence, and the penis returns to the flaccid state.
H I S T O L O G Y
L A B O R A T O R Y
Male Reproductive System
OBJECTIVES:
Upon completion of study of this section the student will be able to:
1. Identify the endocrine and exocrine subdivisions of the testes.
2. Distinguish the cells of the spermatogenic cell lineage.
3. Identify and distinguish among epididymis, vas deferens, urethra, seminal vesicles
and the prostate gland.
4. Describe the structure of the penis and indicate how it becomes tumescent.
ANNOTATIONS
Refer to the Male Reproductive System handout to review the functions and basic organization
of the structures examined in this session.
Human testis, H&E (Harris Biol. H.10-66):

The structure of the tissues resembles that of a grapefruit, a thick skin beneath which
lies membrane separated segments. The testes outer surface is lined by a thin
squamous mesothelium beneath, which is a very dense irregular capsule called the
tunica albuginea. Connective tissue septa subdivide the interior into about 250 lobular
compartments. Centrally the septa merge forming the vascular and nerve rich
mediastinum.

In each lobular compartment a 2-4 coiled and compacted seminiferous tubules. The
tubules are suspended within a loose CT matrix that contains islands of clustered
testosterone secreting interstitial (Leydig cells). The seminiferous tubules are
surrounded by a layer of flattened myoid cells that are closely applied to the basement
membrane. The seminiferous tubule epithelium is stratified (i.e., sperm lineage cells
stacked upon Sertoli cell surface). The predominant cell is the large pyramidal Sertoli
cell, which possesses a large elliptical nucleus with prominent nucleolus.

Large rounded pale cells, with condensed nuclear heterochromatin, toward the luminal
side of the myoid cells are type A spermatogonia. The type B-cells possess a larger,
more euchromatic nucleus.

The next layer of cells toward the lumen are the primary spermatocytes which are the
largest cells and their nuclei almost always show condensed chromosomes.
Secondary spermatocytes are found closer to the lumen, are about half the size of the
primary spermatocytes and are frequently not identifiable because they rapidly divide
and form the spermatids, small rounded cells near the lumen with condensed
heterochromatin.

During spermiogenesis the spermatid nuclei condense and become more pointed. The
heads of these forming spermatozoa are embedded in the Sertoli cells and their flagella
tails extend into the lumen.
Identify and check-off each of the following:
( ) Tunica albuginea
( ) Lobule septum with blood vessels ( ) Interstitial cells
( ) Seminiferous tubules ( ) Sertoli cell
( ) Myoid cell
( ) Type A spermatogonium ( ) Type B-spermatogonium
( ) Spermatozoan
( ) Primary spermatocyte
( ) Secondary spermatocyte
( ) Spermatid
Epididymis, H&E:
 Examine each of the two slides listed compare the structures included in each
section, there might be regions of efferent ductules, portions of the vas deferens or
rete testes included

The epididymus consists of a highly coiled tubule by pseudostratified columnar
epithelium. The lining cells possess numerous stereocilia projecting from their apical
surfaces. Sperm and detached cells are present in the lumen.

The epithelium is contained within a sleeve of smooth muscle. The muscle is thinnest
at the proximal end of the epididymus and becomes three thick layers where it
becomes continuous with the thick musculature of the vas deferens.
Identify and check-off each of the following:
( ) Cross-section of epididymus
( ) Stereocilia
( ) Smooth muscle of muscularis
( ) Spermatozoa
Spermatic cord, H&E (Harris Biol. H.10-651):
 The spermatic cord consists of the vas deferens, blood vessels nerves, the
Pampiniform plexus (temperature regulation) and cremaster skeletal muscle fibers.

The vas deferens is lined by a pseudostratified columnar epithelium, which sits upon
a thick walled muscular tube. There are three muscle layers with cells oriented
longitudinally, circularly and longitudinally with respect to the long axis of the duct.
Muscular contractions of this duct account for most of the ejaculatory pressure.

Look for a plexus of large irregular veins surrounding one or two arteries. This
Pampiniform plexus is a counter current exchange-cooling device to lower blood
temperature. Look for the striated skeletal muscle of the cremaster muscle. Bundles
of basophilic peripheral nerves (in slides from this commercial source, see above)
and adipose are found within the loose CT of the cord.
Identify and check-off each of the following:
( ) Vas deferens
( ) Pseudostratified columnar epithelium ( ) Muscle tunics
( ) Pampiniform plexus ( ) Skeletal muscle
( ) Artery
( ) Vein
Seminal vesicle, H&E (Carolina Biol. H.8700):
5. At low magnification scan the section and identify the complexly folded mucosa lined by
a secretory simple epithelium the folds subdivide the lumen into many irregular
compartments which are all continuous, centrally.
6. The lining epithelial cells sitting on the lamina propria are anywhere from
pseudostratified columnar to low cuboidal in height, depending upon their activity.
The cells secrete about 70% of the fructose-rich semen. This organ is characterized
by the appearance of the complexly folded lumen and thick muscular coat.
Identify and check-off each of the following:
( ) Mucosal folds
( ) CT of lamina propria
( ) Smooth muscle layers
Prostate, H&E:

The prostate, the largest accessory gland in the male, surrounds the urethra from it
origin from the bladder. The gland consists of 30-50 tubuloalveolar glands drained by
20 or more ducts into the prostatic urethra.

The gland is enclosed in a CT capsule subdivided by septa. The glands are
irregularly organized and the lining epithelium may range from pseudostratified to
simple squamous depending on the region and its activity. The lumina of the glands
characteristically possess glycoprotein prostatic concretions, which increase with
age.

The lamina propria surrounding the glands is rich in smooth muscle myocytes. The
prostatic urethra is lined by transitional epithelium containing an eosinophilic apical
cell layer.

The glands are arranged in three strata surrounding the urethra (centrally, beneath
the epithelium are periurethral mucosal glands, medially are the submucosal glands
and peripherally are the more abundant main prostatic glands.
Identify and check-off each of the following:
( ) Prostatic gland ( ) Prostatic concretions ( ) Urethra
( ) Smooth muscle
Penis, H&E (Harris Biol. H10-14):
7. Beneath the thin skin and underlying dermis is a rich, more loosely organized
hypodermis.
8. The hypodermis contains an abundance of blood vessels and peripheral nerves. Within
the dorsal portion of the penile shaft are the two erectile cylinders, the corpora
cavernosa of the penis. Each corpus is ensheathed in an unusually dense CT matrix
called the tunica albuginea. The erectile tissue consists of large venous sinuses
separated by CT trabeculi.
9. The erectile tissue veins are supplied by deep arteries. Beneath the corpora cavernosa
of the penis lies the smaller corpus cavernosum of the urethra. Centrally within this
erectile tissue is the penile urethra. In my slide there is not much erectile tissue
around the urethra, it is mainly comprised of smooth muscle cells.
ldentify and check-off each of the following:
( ) Urethra
( ) Deep artery
( ) Erectile tissue ( ) Corpus cavernosum of the penis
( ) Thin skin
( ) Artery
( ) Vein
H I S T O L O G Y
L E C T U R E
FEMALE REPRODUCTIVE SYSTEM
OBJECTIVES: The complexity of the female reproductive system is reflected in the diversity of
the organs that constitute the system, the interactions of hormones within the system and the
relationship of the system with other organs, notably the hypothalamus and pituitary.
The health care professional must understand the structure and function of the system in order
to treat the clinical problems that are associated with each of the organs of the system. The
areas of clinical interest include carcinomas of the breast, ovary, cervix and uterus, benign
tumors of the breast and fibroid tumors of the uterine myometrium, management of pregnancies
by caring for individuals with normal conception, gestation and delivery and treatment of
persons unfortunate to have an ectopic pregnancy or miscarriage, counseling about birth control
and hormone replacement therapies.
The internal structures of the female reproductive system consist of two ovaries, two oviducts or
Fallopian tubes, the uterus, cervix and vagina.
External organs include the clitoris, labia majora, labia minora and the glands of the vaginal
vestibule.
REFERENCES
The Female Reproductive System is covered in Chapter 22 in Basic Histology and in Chapter
17 in the Gartner and Hiatt atlas.
OVARY
The ovaries are paired organs which lie in the peritoneal cavity and are suspended from the
mesentery by a connective tissue membrane, the suspensory ligament.
The medial poles of the ovaries attach to the uterus by the ovarian ligament.
OVARIAN FUNCTIONS
The ovaries have two main functions:
1) Production of the female germ cells, the ova (oocytes), by the process of oogenesis.
2) Synthesis and secretion of steroid hormones which regulate the maturation of developing
gametes or oocytes and maintain secondary sex organs.
STRUCTURE
The ovary is divided into an outer cortex made of connective tissue and developing oocytes and
inner medulla containing blood vessels and nerves.
Oocytes go through progressive developmental stages in the cortex in structures called follicles
and usually one ovum per month is released from the ovary at ovulation.
After ovulation, the residual supporting cells which remain in the ovaries are transformed into
the corpus luteum which persists for a variable length of time.
If pregnancy occurs, the corpus luteum continues to function until parturition.
If the ovum is not fertilized, the corpus luteum regresses and is infiltrated with fibrous connective
tissue to become the corpus albicans.
Fibrous connective tissue forms a band of variable width called the tunica albuginea (literally,
white coat) which lies under a single layer of cuboidal epithelial cells (arrow) covering the
surface of the ovary.
This epithelial tissue is given the unfortunate name germinal epithelium. The epithelial coat has
nothing to do with the formation of germ cells, but is simply the reflection of the peritoneum over
the ovarian surface.
FOLLICULAR ORGANIZATION
PRIMORDIAL FOLLICLE. Several oocytes in various stages of development are located in the
ovarian cortex. The most primitive oocytes are associated with a single layer of flattened
peripheral cells in structures termed primordial follicles. Oocyte surrounded by a single layer of
squamous cells. The oocyte is called primary oocyte and is in prophase of first meiotic division.
The layer of follicular cells arrests further meiotic activity until after the female is sexually
mature. Meiosis continues during ovulation and fertilization of the ovum.
PRIMARY FOLLICLE : It is the first stage in the development of the growing follicle. Under the
influence of follicle stimulating hormone (FSH) from the pituitary, follicles begin their maturation.
The peripheral, support cells, also known as follicular or granulosa cells, enlarge to form a
single layer of cuboidal cells and the follicle enlarges in size to become the primary follicle. A
layer of glycoprotein (zona pellucida) develops around the oocyte. Microvilli from the oocyte
and the granulosa cells penetrate the zona pellucida, and this appears, at the light microscopic
level, as an increase in stain density in those regions.
Communicating junctions between the oocyte and the granulosa cells have been identified by
electron microscopy. Connective tissue in the immediate vicinity of the primary follicle is
organized into two distinct zones, the theca interna next to the follicular cells and the outer theca
externa continuous with the stroma.
Cells of the theca interna are steroid secreting cells. They have LH receptors and secrete
androgens that are estrogen precursors. As expected the theca interna is a highly vascular
structure.
Further development of primary follicles results from the mitoses of granulosa cells to produce a
multilaminar (many layers of granulosa cells) primary follicle.
SECONDARY FOLLICLE The primary follicle continues its maturation and becomes a
secondary follicle when a fluid filled cavity displaces the follicular cells (also called granulosa
cells). The cavity is known as the antrum, and the follicle is also known as an antral follicle.
Several of these cavities form and coalesce into a single large chamber. The oocyte is
surrounded by several layers of granulosa cells called the corona radiate and the oocyte rests
on a small hill of granulosa cells called the cumulus oophorus.
The antrum contains a hormone-rich fluid secreted by the granulosa cells.
GRAAFIAN FOLLICLE Continued maturation and enlargement of the secondary follicle form a
structure called the Graafian follicle (mature follicle) which exists just prior to ovulation. The
follicle is so large that the entire structure is often not entirely included in histologic sections.
The oocyte and attendant corona radiata granulosa cells rest on a hill of granulosa cells, the
cumulus oophorus.
OVULATION : A surge of luteinizing hormone (LH) from the pituitary occurs at midcycle
causing increased blood flow to the ovaries, edema and release of collagenase in the vicinity of
the mature follicle. The primary oocyte completes the first meiotic division to form the secondary
oocyte and first polar body.
The secondary oocyte enters the second meiotic division and stops at metaphase. The
secondary oocyte and surrounding granulosa cells are released from the ovary.
CORPUS LUTEUM : At ovulation with the release of the ovum and loss of antral fluid,
rearrangement of the granulosa cells and theca interna cells occurs. Hormones from the corpus
luteum (CL) inhibit pituitary LH and FSH preventing ovulation of other follicles. If the individual
becomes pregnant, the corpus luteum is maintained for 4-5 months by placental human
chorionic gonadotropin (HCG). If pregnancy does not occur, the corpus luteum degenerates.
GRANULOSA LUTEIN CELLS : Granulosa cells fill the collapsed antrum and are known as
granulosa lutein cells. These are large, round cells with a central nucleus. They convert
androgens from theca lutein cells into estrogens which they secrete. They also secrete
progesterone.
THECA LUTEIN CELLS: The cells of the theca interna retain their linear characteristics, are
called theca lutein cells, are interspersed between the granulosa lutein cells and are fewer in
number. They secrete progesterone and androgens.
CORPUS ALBICANS : Degeneration of the corpus luteum produces a structure which is
invaded by fibroblasts and phagocytic cells. The corpus luteum becomes fibrotic and the cells
are removed by macrophages resulting in a white scar in the ovary, hence the name corpus
albicans.
ATRETIC FOLLICLE :
Usually one ovum is released from the ovary at ovulation. However, a
number of primordial follicles responded to FSH (or to local factors) and develop concurrently
with the follicle that undergoes ovulation. These remain in the ovary and degenerate to form
atretic follicles in which breakdown of the oocyte, zona pellucida and granulosa cells occurs.
OVARIAN HORMONES
Hypothalamic gonadotropin releasing factors (GnRH) stimulate secretion of pituitary basophil
secretion of FSH early in the cycle and LH at the midpoint.
FSH promotes follicular development and the LH surge causes ovulation and maintains the
corpus luteum.
Estrogen from ovarian follicles can stimulate (+) hypothalamic production of LHRH and inhibit (-)
secretion of the releasing hormone for FSH.
Progesterone and estrogen from the corpus luteum inhibit (-) releasing factor secretions from
the hypothalamus.
Hormone
Source
Gonadotropinreleasing hormone
Function
Stimulates release of FSH and LH from anterior pituitary
Hypothalamus
(GnRH)
Prolactin-inhibiting
Inhibits prolactin release by pituitary Acidophil
factor
Hypothalamus
Follicle-stimulating
Basophils of
hormone
anterior
Stimulates secretion of estrogen and development of
ovarian follicles (from secondary follicle onward)
pituitary
Luteinizing
Basophils of
Stimulates formation of estrogen and progesterone;
hormone (LH)
anterior
promotes ovulation and formation of corpus luteum
pituitary
Estrogens
Granulosa
Inhibits release of FSH and GnRH; triggers surge of LH;
cells of the
causes proliferation and hypertrophy of myometrium of
ovary
uterus; causes development offemale sexual
granulosa-
characteristics, including breasts and body fat
lutein cells of
the
corpus
luteum; and
placenta
Progesterone
Granulosa
Inhibits the release of GnRH from the hypothalamus
cells of the
theca-lutein and
ovary;
LH from the basophils of the anterior pituitary;
granulosa-
causes the development of the uterine endometrium and
lutein cells of
regulates the viscosity of mucus produced by the glands
the corpus
of the uterine cervix; causes development of female
luteum; and
sexual characteristics including breasts
placenta
Inhibin
Granulosa
Inhibits FSH secretion by basophils of the anterior
cells of the
pituitary
and
ovary;
granulosalutein cells
Activin
Granulosa
Stimulates FSH secretion
cells of the
ovary
Human chorionic
Placenta
gonadotropin(hCG)
Human placental
promotes the release of progesterone
Placenta
lactogen
Relaxin
Assists in the maintenance of the corpus luteum;
Promotes mammary gland development during
pregnancy; promotes lactogenesis
Placenta
Facilitates parturition by softening the fibrocartilage
of the pubic symphysis; softens the cervix and
facilitates its dilation in preparation for parturition
Oxytocin
Hypothalamus Stimulates smooth muscle contraction of the uterus
via the
during orgasm and during parturition; stimulates
posterior
contraction of myoepithelial cells of the mammary
pituitary
gland assisting in milk ejection
Polycystic Ovarian Syndrome
A disorder in which the ovaries are bilaterally enlarged with multiple follicular cysts due to
abnormal regulation of the hypothalamic-pituitary-ovarian axis. Symptoms include amenorrhea,
menstrual abnormalities, infertility, and hirsutism.
Polycystic Ovaries develop when the ovaries are stimulated to produce excessive amounts of
male hormones (androgens), particularly testosterone, either through the release of excessive
luteinizing hormone (LH) by the anterior pituitary gland or through high levels of insulin in the
blood (hyperinsulinaemia) in women whose ovaries are sensitive to this stimulus.
This syndrome acquired its most widely used name because a common sign is multiple (poly)
ovarian cysts. These form where egg follicles matured but were never released from the ovary
because of abnormal hormone levels.
OVIDUCT
The oviducts are a pair of fibromuscular tubes that extend from the ovary to the uterus. Regions
near the ovary have a well-developed mucosa while those near the uterus have a thick
muscular wall. The oviduct which is also called the uterine or Fallopian tube conducts ova
expelled from the ovary to the uterus.
The oviduct has four distinct segments. The area closest to the ovary has a funnel shaped
opening and is known as the infundibulum. The next region, the ampulla, is the longest
segment and leads to a short isthmus which is adjacent to the uterus. The last segment of the
oviduct is embedded in the wall of the uterus and is the intramural or uterine portion of the tube.
Each one of these segments has a histology which is slightly different from the other.
The mucosa of the oviduct is thrown in to longitudinal folds which is exaggerated in
infundibulum and ampulla. They divide the lumen into labyrinthine spaces. The inner circular
and outer longitudinal bands of smooth muscle in the oviduct serve to move the ovum toward
the uterus.
OVIDUCT CELLS
Two distinct types of cells occupy the mucosa: ciliated simple columnar epithelial cells and
secretory cells. The latter are wedged in between the ciliated cells and as a result are also
called peg cells. They are nonciliated and produce a fluid that provides nutritive material for
ovum.
The ciliated cells keep the fluids secreted by the peg cells in motion . Research suggests that
both ciliary movements and peristaltic muscular activity are involved in the movement of the
oocyte.
UTERUS
A muscular organ which functions to provide a protective and nutritive environment for the
developing fetus. It is made up of three parts Fundus , body and cervix. The wall of the uterus
is made of three layers; the outer perimetiurm lined by serosa or adventitia; a thick smooth
muscle layer called myometrium; and an inner endometrium.
The myometrium is composed of interlacing bands of smooth muscle fibers which contract
under the influence of oxytocin at parturition. They undergo Hyperplasia and hypertrophy during
pregnancy.
Uterine fibroids (also called leiomyomas or myomas) are benign growths of the muscle inside
the uterus. They are not cancerous, nor are they related to cancer. Fibroids can cause a wide
variety of symptoms, including heavy menstrual bleeding and pressure on the pelvis. About 25%
of women in their reproductive years have noticeable fibroids.
Part of the endometrium is lost in the menstrual flow and is rebuilt during each cycle.
The endometrium is divided into functional (decidua functionalis) and basal (decidua basalis)
regions. The functional area changes dramatically during the course of each cycle and is lost if
pregnancy does not occur. The basal portion is close to the myometrium and is retained during
menstruation to serve as stem cells for the functionalis during the next cycle.
PROLIFERATIVE STAGE:
The morphology of the endometrium changes during the menstrual cycle. It increases in height
during the first part of the ovarian cycle, is maintained for a while and then is reduced to a basal
level if the ovum is not fertilized.
There are three stages of endometrial cycling. Following the cessation of menstruation, the
endometrium goes through a proliferative phase in which glands and blood vessels increase in
size, and this occurs under the influence of estrogen from the ovary.
Under the influence of ovarian estrogen, the uterine endometrium lengthens during the
proliferative stage of uterine development. Uterine tissues, both glandular and stromal tissues,
proliferate. During this stage the glands are relatively straight and have the same type of simple
columnar epithelial tissue as that at the surface.
In the epithelium of a uterine gland, these nonciliated simple columnar epithelial cells accumlate
glycogen.
Blood vessels called spiral arteries lengthen and coil slightly.
SECRETORY STAGE
During the next phase, the secretory phase, the endometrium attains its greatest height and is
capable of supporting the fetus should fertilization and implantation occur. Progesterone from
the corpus luteum main-tains the endometrium.
Should fertilization not occur, much of the endometrium is lost in the menstrual phase and is
reduced to a small area near the myometrium.
The secretory phase of the uterus commences with ovulation. During the secretory phase, both
the spiral arteries and endometrial glands continue their development as the endometrium
elongates. Under the influence of progesterone from the corpus luteum, the endometrium
prepares itself to receive the fertilized ovum. It is during this phase that the endometrium is
tallest in anticipation of a potential implantation.
The surface columnar epithelium present in the proliferative stage persists. Endometrial glands
become cork-screw in shape, and the lining cells secrete nutrients, especially glycogen, into the
lumen. This dilates the glandular lumen.
Spiral arteries continue to lengthen, become coiled and extend almost to the surface.
MENSTRUAL STAGE
In the menstrual phase of the uterine cycle, the stroma has become engorged with blood. The
walls of the blood vessels become leaky and the glandular epithelium degenerates. The entire
functionalis is lost during menstruation, and only the basal layer of the endometrium persists as
a small area of tissue adjacent to the myometrium.
The uterine stromal tissue indicates the presence of erythrocytes and there is accumulation of
leukocytes in the lumens of the glands.
CERVIX
The neck of the uterus or cervix extends into the vaginal canal. The portion of the cervix
extending into the vagina and lined by stratified squamous non keratinized epithelium is the
called the ectocervix. Mucous membrane lining the cervical canal and the region of the opening
of the cervical canal into the uterine cavity is called the endocervix.
The wall of the cervix contains dense connective tissue and relatively little smooth muscle as
compared to the uterus. Mucus secreting glands are located in the irregular outlines of the
mucosa. Ducts from these glands can become occluded, and, as a result, the mucus dilates the
lumen of the gland to form cysts ( Nabothian cysts). The cervix protects the uterus from
bacterial infections and dilates during parturition to permit passage of the fetus.
The cervical mucosa is lined by stratified squamous epithelium at its opening into the vagina,
the porto vaginalis, and by simple columnar epithelium near its junction with the uterus proper,
the ostium of the cervix. The columnar epithelium is not lost during menstruation.
Cervical mucus exhibits changes in viscosity during the menstrual cycle. In the uterine
proliferative phase, estrogen promotes the secretion of watery mucus which allows passage of
spermatozoa into the uterus. After ovulation, the mucus secretions are more viscous to prevent
the spread of bacteria.
The squamous epithelial cells of the cervix are constantly being shed into the vagina.
Specially stained preparations of these cells form the basis of Papanicolaou (pap) smears which
can be used to diagnose the state of health of the cervix and can determine the presence of
cervical carcinoma.
The Transformation Zone (T zone) is located between the original squamo-columnar junction
and the junction between the newly formed squamous metaplastic epithelium and the
endocervical columnar epithelium. All cervical precancerous lesions develop from this zone.
Invasive carcinoma of cervix: Malignant cells breach the basement membrane and invade local
tissues and then to distant places.
VAGINA
The vagina is a fibromuscular canal extending from the cervix to the vestibule of the external
genital organs is lined with stratified squamous epithelium that is not keratinized. Under the
base-ment membrane of the epithelium is a lamina propria of connective tissue which is densely
fibrous near the epithelium and becomes less dense near the smooth muscle. Elastic fibers are
located just under the epithelium. The vagina does not contain glands.
The wall of the organ is formed primarily of smooth muscle which is arranged in two indistinct
layers consisting of inner circular and outer longitudinal coats. Striated muscle fibers may be
present at the opening of the vagina at the vestibule. An adventitia of dense connective tissue
lies outside of the muscle layers.
During the follicular phase of the menstrual cycle, the epithelial cells of the vagina store
glycogen. The glycogen is washed out of the cells in the preparative procedures for light
microscopy, and as a result the outer layers of cells appear pale with small darkly stained
nuclei.
MAMMARY GLANDS
Compound tubuloalveolar glands that lie in the superficial connective tissue of the thorax.
Glandular elements are arranged in a radial fashion around the nipple into which ducts from the
secretory units empty.
Mammary gland histology varies with age and the physiological state of the individual. They
attain their greatest morphological and functional development near the end of pregnancy and
during the period of lactation. Their structure and function are affected by a variety of hormones
from the ovary, placenta and pituitary.
The epithelial cells in the alveoli in the nonpregnant individual are considered as elements of the
duct system. Upon pregnancy these cells proliferate and, in the late stages prior to delivery of
the fetus, become secretory.
The ducts are lined by cuboidal or columnar cells and subtle changes in the ducts occur during
the ovarian cycle. Early in the cycle the ducts appear as flattened cords of cells. Under the
influence of estrogen, definitive lumens appear in the ducts and the potential secretory cells
elongate.
INACTIVE GLAND
In inactive mammary glands, little, if any, secretions are produced by the alveolar cells. The
flattened nuclei of fibroblasts are found in the connective tissue between the alveoli.
PROLIFERATING GLAND
As a result of the influence of estrogen and progesterone from the
corpus luteum and placenta, the duct cells and secretory cells proliferate.
Growth and development of the mammary glands during pregnancy are also dependent on
prolactin which is produced by the anterior pituitary, by human placental lactogen
(somatomammotropin), by adrenocorticoids and thyroid hormone.
During the proliferative phase of breast development, the expanding epithelial secretory units fill
the connective tissue between other units. The connective tissue within the secretory cluster
exhibits an increase in cellularity from the infiltration of lymphocytes and proliferation of other
cells. The developing secretory cells are arranged in two layers as a stratified cuboidal
epithelium around a central lumen forming what will become, in the active gland, the alveoli.
As pregnancy progresses, proliferation of secretory alveoli and duct cells continues at the
expense of the connective tissue in the breast. Alveoli lined by cuboidal cells enlarge and
begin secreting a protein-rich material called colostrum which expands the alveolar lumen.
Colostrum accumulates in the lumen of the glands and ducts and is the first secretion of the
mammary glands provided to the newborn. The presence of antibodies, especially
immunoglobulin A (IgA), from the mother imparts a passive immunity to the infant. During
pregnancy the increased numbers of alveoli displace the connective tissue between the
secretory elements.
LACTATING GLAND
The morphology of the lactating gland is slightly different from the images of the gland in late
pregnancy. As the result of the influence of prolactin from the adenohypophysis, the alveolar
cells secrete milk proteins and other nutrients and proteins, especially immunoglobulin A (IgA),
into the expanded alveoli which compress the secretory cells somewhat.
The lactating gland appears morphologically similar to the thyroid or the lung because of this
activity. The presence of a well developed system of ducts allows the lactating mammary gland
to be distinguished from either of these two organs.
Ducts and glands attain their greatest development during the last stages of pregnancy. The
lumen of the glands is filled with their secretions.
The myoepithelial cells of the lactating gland are stimulated to contract by oxytocin released
from the neurohypophysis in response to suckling. Contractions of myoepithelial cells force milk
from the alveoli into the duct system.
Prolactin secretion and milk production continue as long as the child suckles. Weaning from the
breast results in regression of breast tissue and resumption of the ovarian cycle which was
suppressed by the process.
The ducts of the mammary gland merge into fifteen to twenty lactiferous ducts that open at the
nipple. The ducts are surrounded by dense connective tissue under the stratified squamous
epithelium at the surface.
Sebaceous glands, without associated hair follicles, are located in the dermis just below the
epithelium. The glands open either onto the surface or into ducts. Their secretions lubricate the
nipple during suckling. Free nerve endings and touch receptors (Meissner's corpuscles) are
found in the dermal papillae.
NONINVASIVE INTRADUCTAL CARCINOMA OF THE BREAST:
Tumors, both benign and malignant neoplasms, constitute the majority of clinical disorders of
the breast. Tumors can arise from a variety of sources, from epithelial tissue, glandular and
ductal tissue, fibrous connective tissue and adipose tissue. The list of potential diseases
extends from benign lipomas and fibromas to invasive and noninvasive carcinomas.
Carcinoma of the breast is responsible for 20% of all the deaths by cancer of women. There are
two major classes of breast cancer, noninvasive carcinomas and invasive or infiltrating
carcinomas; each has several subclasses. Noninvasive intraductal carcinoma, constitutes
about 20-30% of all breast cancers. It is characterized by the spread of malignant cells in the
duct system. These cancer cells do not have the ability to cross the ducts’ basement
membrane and do not metastasize. Vacuoles are in the epithelium and tumor cell clusters.
PLACENTA
The placenta functions in the exchange of material between the fetus and the mother and in the
secretion of hormones important for the maintenance of pregnancy and the developing fetus.
It is made up of two parts, the fetal part and the maternal part.
The maternal part of the placenta is the decidua basalis of the endometrium containing
anchoring villi, large decidual cells and a typical connective tissue stroma. The decidua basalis
also conatins basal portions of uterine glands.
The amniotic surface is lined by simple squamous cells deep to which is the connective tissue of
the chorion. Deep to the connective tissue layer are the trophoblast cells of the chorion. The
trophob;ast and the umderlying connective tissue form the chorionic plate. The anchoring villi
arise from the chorionic plate, extend to the uterine wall and attach to the decidua basalis.
Floating villi extend from the anchoring villi and float in the intervillous space which is bathed
with maternal blood.
DECIDUAL CELLS
Following implantation, the cells of the uterine stroma enlarge and
proliferate to form the bulk of the endometrial tissue.
These are decidual cells and have pale staining nuclei with one or more nucleoli. Their
cytoplasm contains numerous mitochondria and areas of rough endoplasmic reticulum. They
provide nutrients to the developing embryo and secrete a hormone similar to pituitary prolactin
which helps maintain the corpus luteum.
CHORIONIC VILLUS
Each chorionic villus has an outer syncytiotrophoblast layer of
basophilic cells which have a brush border of microvilli at their surface to increase the
absorptive area. The syncytiotrophoblastic cells secrete human chorionic gonadotrophin which
maintains the corpus luteum of pregnancy following the decrease in luteinizing hormone
secretion from the pituitary. In addition, syncytiotrophoblasts produce human chorionic
lactogenic hormone which may aid in the stimulation of milk production in the mammary gland.
Syncytiotrophoblastic cells secrete progesterone and estrogen as well.
Each villus has a basal lamina which separates the epithelium from the subjacent core of loose
connective tissue. Within the connective tissue core of the villi are branches of the umbilical
arteries and vein. Fibroblasts and phagocytic cells (Hofbauer's cells) are also found there.
The spaces between the villi are bathed by maternal blood. Nutrients are removed from the
blood and wastes are excreted into the maternal blood.
Immediately below the syncytio-trophoblast layer are the cyto-trophoblast cells which are
abundant in the early stages of pregnancy. In the placenta at term the number of cells in this
layer is greatly reduced. The cytotrophoblastic cells most likely serve as a stem cell population
for the syncytiotrophoblastic cells.
UMBILICAL CORD conducts vessels to and from the developing fetus, brings nutrients to the
child and carries waste products away. The cord is lined with simple cuboidal epithelium similar
to that of the amnion. Beneath the epithelium is mucous connective tissue containing
fibroblasts, collagen fibrils and a gel-like matrix called Wharton's jelly.
The umbilical cord has two arteries and one vein. The arteries convey wastes away from the
fetus, and the veins bring nutrients and other materials to the fetus.
The gel-like consistence of the mucous connective tissue imparts flexibility to the umbilical cord.
Elongated fibroblasts and collagen fibrils form the bulk of the cord matrix.
H I S T O L O G Y
L A B O R A T O R Y
Female Reproductive System
OBJECTIVES:
At the completion of this section, the student will be able to:

Identify the tissues of the ovary, and distinguish between primordial, primary,
secondary, tertiary and atretic follicles.

Describe the three layers of the uterine tube and compare the structure in the
different regions along its length.

Describe the three layers of the uterus. Understand the morphological changes in
the endometrium and myometrium during the normal menstrual cycle and during
pregnancy.

Compare the structures and functions of the mammary gland at different stages.

Identify the three layers of the cervix and the vagina.

Identify the villi and intervillous space in the placenta. Relate these structures with
placental function.
Laboratory Experience
The purpose of this laboratory exercise is to identify the different tissues and cells found in the
female reproductive system. Identify the cell types present and the tissue structure in each of
the different organs. Use the slides listed below along with your manual, your text and your
atlas to identify the cells, tissues and organs described.
Ovary (#87) and Corpus Luteum (#88):
Scan the section at low magnification. At the periphery, the ovary is lined by a simple
cuboidal mesothelium, the germinal epithelium. Beneath the mesothelium is a layer
of fibrous tissue, the tunica albuginea. Underlying the tunica albuginea is the less
fibrous stroma and scattered within it are ovarian follicles. These structures
constitute the ovarian cortex. In the center of the ovary is the medulla composed of
loose connective tissue with large blood vessels and lymphatics.
Ovarian follicles (found only in the cortex) are composed of an oocyte encircled by
epithelia-like follicular (granulosa) cells. Be aware that all follicles are not cut through
the center, many sections just graze the surfaces of follicles so that their stages may
be difficult to distinguish. Borrow slides if necessary to see each of the following
follicular stages:
1) Primordial follicles consist of flat follicular cells surrounding a primary
oocyte.
2) Primary follicles have one or more layers of cuboidal follicular cells
surrounding a primary oocyte. A thin zona pellucida lies between the oocyte
and the follicular cells.
3) Secondary (antral) follicles have a thick granulosa (follicle cell layer) and a
zona pellucida. They are distinguished by an antrum filled with liquor folliculi.
The hillock of follicle cells that attach the oocyte to the follicle wall is called
the cumulus oophorus. Around the periphery of the follicle are stroma cells
which comprise the theca interna. The flattened spindle-shaped cells of the
theca externa may also be apparent. This layer can be less distinctly visible.
4) Tertiary (Graafian / mature) follicles have a large antrum, and a thin
granulosa layer. The mound-like cumulus oophorus will attach the zona
pellucida-encapsulated oocyte to the follicle wall. Follicle cells that form a
ring around the surface of the oocyte are called the corona radiata. Both
layers of the theca are much more evident.
5) Atretic follicles are degenerating follicles and may arise during any
developmental stage.
The corpus luteum is a large group of yellowish cells from the wall of a tertiary follicle
after the oocyte is ovulated. It is comprised mainly of granulosa lutein cells derived
from the granulosa of the follicle and a smaller layer of theca lutein cells derived from
the former theca interna. It serves as a temporary endocrine gland which persists for
about 2 weeks. If fertilization and implantation occurs, it persists for several months.
The corpus albicans is white, fibrous scar tissue that remains in the ovary after the
corpus luteum has degenerated.
Identify and check-off each of the following:
( ) Germinal epithelium
( ) Primordial follicle
( ) Tertiary follicle
( ) Zona pellucida
( ) Corpus albicans
( ) Tunica albuginea ( ) Cortex
( ) Medulla
( ) Primary follicle
( ) Secondary follicle
( ) Granulosa cell
( ) Theca Interna
( ) Antrum
( ) Cumulus oophorus
( ) Corpus luteum
Uterine (Fallopian) Tube / Oviduct (#86):
The proximal end of the uterine tube is near the ovary, where it opens and displays
finger-like processes called fimbriae. The tube is loosely subdivided into 4 zones: the
infundibulum with fimbriae nearest the opening; the ampulla (a short, thin-walled
section); the longest segment, the isthmus which narrows into the intramural
portion within the muscular wall of the uterus.
All of the regions have the same layers, but proximally the mucosa is more highly
folded than distally. Proximally the simple columnar epithelium contains more
ciliated cells than Peg cells; distally, this ratio is reversed. Peg cells secrete a
serous fluid into the lumen. Ciliated cells create currents that facilitate egg and sperm
transport. The lamina propria is well vascularized and may contain lymphocytes.
Beneath the lamina propria is the muscularis. The inner layer is primarily circular
smooth muscle and the outer layer is primarily longitudinal. The serosa is vascular
loose connective tissue covered by a simple squamous mesothelium.
Examine the slide at low magnification; compare the mucosa with regard to diameter
and number of folds. At high magnification, compare the number of ciliated versus
secretory cells in the epithelium. Examine the lamina propria and the muscularis.
Identify and check-off the following:
( ) Mucosa
( ) Lamina propria
( ) Smooth muscle / muscularis
( )Secretory peg cells
( ) Ciliated cells
Uterus (#90):
The wall of the uterus has 3 structurally and functionally distinct layers:
1) Perimetrium is the outermost layer composed of dense irregular connective
tissue.
2) Myometrium is the middle and thickest layer comprised of interwoven layers of
smooth muscle. Cyclic changes in cell numbers and size are mediated by the
estrogen / progesterone balance. The myometrium is responsible for muscular
support and for uterine contractions during partruition.
3) Endometrium is analogous to the mucosa and is lined by simple columnar
epithelium with many ciliated cells and simple tubular glands rich in mucus secreting
cells. The epithelium is underlain by a lamina propria. The endometrium is divided
into a basal layer adjacent to the myometrium and a functional layer. The functional
layer varies in thickness with stages of the menstrual cycle and is sloughed off during
menstruation.
Large blood vessels supply the uterus. Branches called straight arteries supply the
basal layer of the endometrium and these branch to form spiral arteries which
supply the functional layer. Spiral arteries constrict when progesterone / estrogen
levels drop prior to menstruation. This results in lack of blood flow and leads to
ischemia and shedding of the functional layer during menstruation.
Both the uterus, and its stage in the menstrual cycle are identified by examining the
endometrium. The proliferative phase has a relatively thin endometrium with short,
straight glands. The secretory phase is characterized by a thick endometrium with
noticeably elongated, widened, and coiled glands.
Secretions may be visible in the uterine lumen and in the apical vacuoles of epithelial
cells. The menstrual phase is characterized by stagnant pools of blood in distended
vessels.
Identify and check-off each of the following:
( ) Endometrium
( ) Basal layer
( ) Uterine glands
( ) Myometrium
( ) Perimetrium
( ) Lamina propria
( ) Functional layer ( ) Simple columnar epithelium
( ) Proliferative stage
( ) Secretory stage
Cervix:
Although no slides of the cervix exist in your slide box, you should be familiar with
the histology of the cervix. Examine your text and atlas for information on the cervix.
The narrow end of the uterus projects into the vagina and forms the short, tubular
cervix. As it projects into the vagina, the cervical mucosa changes from a simple
columnar epithelium to a stratified squamous epithelium.
The glands in this region are called cervical glands; they secrete mucus whose
consistency changes throughout the menstrual cycle. Estrogen stimulates production
of a thick and viscous secretion which restricts entry of pathogens to the uterus. At
ovulation, the secretions become watery to facilitate sperm entry. Progesterone
stimulates production of a thick mucus that creates a cervical plug.
Also under influence of estrogen, the cervix swells, exposing the uterine epithelium
near the os of the cervical canal to the vaginal environment. This results in localized
metaplasia; the columnar epithelium becomes squamous and monthly metaplasia
may produce transformed cells which seed cervical cancer. Pap smears are made
from cell scrapings taken from the area and are used to diagnose potentially
cancerous cells. Early detection and treatment effectively reduces mortality rates for
cervical and uterine cancer.
Identify and check-off each of the following:
( ) Vaginal stratified squamous epithelium ( ) Uterine simple columnar epithelium
( ) Vaginal / uterine epithelial transition zone
( ) Cervical glands
Vagina (#85):
Scan the slide at low magnification and identify the mucosa which consists of a nonkeratinized, stratified squamous epithelium underlain by a thick, fibroelastic
lamina propria containing lymphocytes. The relatively thick epithelium is interdigitated with tongues of lamina propria, an organization that increases surface
adhesion. As the epithelial cells mature, they approach the surface, become
vacuolated and release glycogen. The glycogen is converted into lactic acid by
resident bacteria producing an acidic lumenal space. Flattened surface cells
continuously detach from the apical surface and are seen in vaginal smears.
Beneath the lamina propria is the muscularis which contains bundles of smooth
muscle interwoven with a dense, fibrous matrix of connective tissue that is
continuous with the adventitia.
Identify and check-off each of the following:
( ) Mucosa
( ) Epithelium
( ) Lamina propria
( ) Muscularis
Placenta (#89):
As the zygote implants in the endometrium, its trophoblast cells proliferate and the
placenta becomes a syncytium of placental villi interdigitated with the intervillous
space containing maternal blood (supplied by the spiral arteries of the uterus). The
placental villi project into the intervillous space and facilitate waste and nutrient
exchange between the embryo and the mother. The villi contain a core of connective
tissue overlain by cytotrophoblast cells. Some villi form large trunks which serve as a
base for the smaller, more numerous villi involved with exchange. Villi that penetrate
the syncytium and bind directly to uterine tissue are called anchoring villi.
Identify and check-off each of the following:
( ) Placental villi
( ) Intervillous space
( ) Cytotrophoblast cells
Inactive (Quiescent) Mammary Gland (Breast) (#92):
At low magnification, the section is primarily composed of dense irregular connective
tissue, islands of inactive lactiferous ducts, clusters of unilocular adipose tissue, and
blood vessels.
Scattered throughout the field are islands of intralobular lactiferous ducts. These
are within lobules and have few secretory or alveolar units. The intralobular ducts are
lined by simple cuboidal epithelium, but the epithelium may look stratified due to the
presence of myoepithelial cells along the basal aspect. Myoepithelial cell nuclei
contain condensed chromatin, and are triangular compared to the pale, round nuclei
of the cuboidal cells. They may be difficult to discern on your slide.
Identify and check-off each of the following:
( ) Lactiferous ducts
( ) Adipose tissue
( ) Simple cuboidal epithelium
( ) Myoepithelial cells
( ) Dense irregular connective tissue
Lactating Mammary Gland (Breast) (# 91):
At low magnification, the epithelium of the ducts is readily distinguished from the
connective tissue. Lobules and large intralobular lactiferous ducts are surrounded
by connective tissue.
Each lobule has numerous distended alveoli that have proliferated along the length
of the intralobular duct that contain lipid, protein and polysaccharide secretion
products in their lumens. Intralobular ducts are smaller branches of the lactiferous
ducts. Secretory epithelial cells are relatively large, slightly basophilic and have a
vacuolated cytoplasm. Plasma cells are may be seen in the vascular lamina propria
within the lobules. Flattened myoepithelial cells can also be observed beneath the
secretory cells.
Identify and check-off each of the following:
( ) Secretory alveoli
( ) Myoepithelial cells
( ) Lactiferous ducts
( ) Secretory cells
Study Questions:
What is the function of myoepithelial cells?
What mode(s) of secretion are used by the glandular tissue of the breast?
List the order of development of ovarian follicles.
What is the role of glycogen release in the vagina?
List the two types of epithelia found at the cervico-vaginal junction.
Which layer of the endometrium is lost during menstruation?
Which of the ovarian follicles does not contain a zona pellucida?
List the epithelia found in the oviducts, in the uterus, in the cervix and in the vagina.
What is found in the intervillous space of the placenta?
FEMALE REPRODUCTIVE SYSTEM WORKSHEET
FILL IN THE BOXES
Structure
Ovary
Primordial follicle
Primary follicle
Secondary (antral)
follicle
Tertiary (mature /
Graffian) follicle
Identifying features
(relevant layers, epithelia, and / or unique
components)
Clinical relevance
(tests, diseases, morphological
changes)
Structure
Corpus luteum
Corpus albicans
Oviduct
Uterus
Cervix
Vagina
Mammary gland
Identifying features
(relevant layers, epithelia, and / or unique
components)
Clinical relevance
(tests, diseases, morphological
changes)