Do I REALLY

Need Histology to
be A Doctor?

Female Reproductive
System
Histology
Department

Introducti
on

Six major functions :

1. Production of female gametes, the ova

2. Reception of male gametes, the
spermatozoa
3. Provision of a suitable environment for
fertilization of ova by spermatozoa
4. Provision of an environment for
development of the fetus
5. A means for expulsion of developed
fetus to the external environment
6. Nutrition of the newborn

Three structural
units on the basis
of function:
1. The ovaries
2. The genital tract
3. The breasts

Introduction
INTERNAL PARTS :

OVARIES
OVIDUCT
UTERUS
VAGINA

FERTILIZATION
AND DEVELOPMENT

EXTERNAL PARTS :

OPENING OF THE VAGINA

LABIA (MAJORA & MINORA)
DELIVER AND EXIT
VESTIBULE
CLITORIS
NOTE : ALTHOUGH NOT GENITAL
ORGANS, THE MAMMARY GLANDS ARE
IMPORTANT ACCESSORY ORGANS OF THE
FEMALE REPRODUCTIVE TRACT.

ANATOMICAL INTEGRATION FOR

REPRODUCTION

Schematic Drawing of Ovary

in Reproductive Age

Picture taken from Basic

Histology Text & Atlas , 10th
edition, L. Carlos Junquira
MD, Jose Carneiro MD, Robert
O. Kelley PhD, Lange Medical
Books, Mc Graw-Hill , 2003.

Ovary

GROSS ANATOMY:

PAIRED OVAL BODIES THAT LIE ON EACH

SIDE OF THE UTERUS

2 DISTINCT ANATOMICAL REGIONS:

COVERED BY A MESOTHELIUM THAT

CONTINUOUS With MESOVARIUM
SQUAMOUS CELLS BECOME CUBOIDAL
AND FORM THE SURFACE EPITHELIUM OF
THE OVARY = GERMINAL EPITHELIUM (OLD
TERM)
MEDULLARY-HIGHLY VASCULAR, CT,
LYMPHATICS AND NERVES
CORTEX-FOLLICLES, CT, AND SOME
SMOOTH MUSCLE
TUNICA ALBUGINEA TO SEPARATE
EPITHELIUM FROM CORTEX

Histology of
Ovary
Part of an ovary
with cortical &
medullary regions.
H&E stain.
Low magnification
Picture taken from Basic Histology
Text & Atlas , 10th edition, L.
Carlos Junquira MD, Jose
Carneiro MD, Robert O. Kelley
PhD, Lange Medical Books, Mc
Graw-Hill , 2003.

Low mag - entire ovary

CL Corpus luteum; F Follicles;

H = Hilus; L Ligament; M - medulla
ERDS & LDL

Cortical region of an ovary

Ovary surrounded by germinal
epithelium & by tunica
albuginea
Groups of primordial follicles,
each formed by an oocyte
surrounded by a layer of flat
follicular cells, are present in the
ovarian connective tissue
(stroma).
Giemsa stain. Low
magnification.
Picture
taken from Basic Histology Text &
Atlas , 10th edition, L. Carlos Junquira MD,
Jose Carneiro MD, Robert O. Kelley PhD,
Lange Medical Books, Mc Graw-Hill , 2003.

Ovarian Surface
epithelium
Neoplasm

Follicles
developme
nt

Ovarian
follicle

Primordial
follicles
Located in the cortex just
beneath tunica albuginea.
One layer of flattened follicular
cells surround the oocyte
(about 30 m in diameter).
The nucleus of the oocyte is
positioned eccentric in the cell.

It appears very light and contains

a prominent nucleolus.
Most organelles of the oocyte
aggregate in the centre of the cell,
where they form the vitelline body
(probably not visible in any of the
available preparations).

Formed by:
an oocyte &
one layer
of cuboidal
ranulosa cells

Pararosaniline
toluidine blue
(PT) stain.
Low
magnification.

Formed by:
An Oocyte &
flat follicula
cells
Picture taken
from Basic
Histology Text &
Atlas, 10th
edition, L. Carlos
Junquira MD,
Jose Carneiro
MD, Robert O.
Kelley PhD,
Lange Medical
Books, Mc GrawHill , 2003.

Primordial Follicles

Primordial Follicles

Primary Follicle
Primary Follicle

ERDS & LDL

The primary
follicle
The first morphological stage that marks the onset of
follicular maturation
The previously flattened cell surrounding the oocyte now
form a cuboidal or columnar epithelium surrounding the
oocyte.
Cytoplasm may have a granular appearance (granulosa
cells).
The continued proliferation of these cells will result in the
formation of a stratified epithelium (with a distinct
basement membrane) surrounding the oocyte.
The zona pellucida (glycoproteins between interdigitating
processes of oocyte and granulosa cells) becomes
visible.
Parenchymal cells of the ovary surrounding the growing
follicle become organised in concentric sheaths, the
theca folliculi.

Late primary Follicle

Stratified Follicular
Epithelium

Oocyte

Zona
Pellucida

ERDS & LDL

Secondary follicle

Small fluid-filled spaces become visible between the granulosa cells as

the follicle reaches a diameter of about 400 m.
These spaces enlarge and fuse to form the follicular antrum (the
defining feature of the secondary follicle).
The oocyte is now located eccentric in the follicle in the cumulus
oophorus, where it is surrounded by granulosa cells.
The theca folliculi differentiates with the continued growth of the follicle
into a theca interna and a theca externa.
Vascularization of the theca interna improves

The spindle-shaped or polyhedral cells in this

layer start to produce oestrogens.

The theca externa retains the characteristics of a highly cellular connective

tissue with smooth muscle cells.

The oocyte of the secondary follicle reaches a diameter of about 125

m.
The follicle itself reaches a diameter of about 10-15 mm.

A small part of wall of

antral follicle:
Antrum
Granulosa cells
Thecas interna &
externa
A basement membrane
separates the granulosa
layer from the theca
interna.

PT stain. High magnification.

An antral follicle:
Oocyte surrounded by granulosa
cells of corona radiata &
supported by cumulus oophorus.
The remaining granulosa cells
form wall of follicle & surround
large antrum.
A theca surrounds the whole
follicle.

Early Secondary Follicle

*
* Developing
Antral Cavity

Thecas
ERDS & LDL

Mature or tertiary or preovulatory or

Graafian follicle
Increases further in size (in particular in
the last 12h before ovulation).
The Graafian follicle forms a small
"bump" on the surface of the ovary, the
stigma (or macula pellucida).
The stigma is characterised by a thinning of
the capsule and a progressive restriction of
the blood flow to it.

Prior to ovulation the cumulus oophorus

separates from the follicular wall.
The oocyte : floating freely in the
follicular antrum.
It is still surrounded by granulosa cells
which form the corona radiata.

The follicle finally ruptures at the stigma

and the oocyte is released from the
ovary

Secondary Follicle

Graafian Follicle

Thecas

Antral
Cavity
Corona
Radiata

Cumulus
Oophorus

ERDS & LDL

Corona Radiata

Zona Pellucida

Cumulus Oophorus

Oocyte

ERDS
& LDL
High Mag Graafian
Follicle

Theca Interna

Atresia
Atresia is the name for the degenerative
process by which oocytes (and follicles) perish
without having been expelled by ovulation.
Only about 400 oocytes ovulate - about 99.9 %
of the oocytes that where present at the time
of puberty undergo atresia.
Atresia may effect oocytes at all stages of their
"life" - both prenatally and postnatally.
By the sixth month of gestation about 7 million
oocytes and oogonia are present in the ovaries.
By the time of birth this number is reduced to
about 2 million. Of these only about 400.000
survive until puberty.
Atresia is also the mode of destruction of
follicles whose maturation is initiated during
the cyclus (10-15) but which do not ovulate.
Atresia is operating before puberty to remove
follicles which begin to mature during this
period (none of which are ovulated).

Characteristic of FOLLICLE ATRESIA

1.Loss of cells of corona radia

2.Oocyte floating free
within antrum

3. Death of granulosa cells,

many of which are seen
loose in antrum
PT stain.
Medium magnification
Picture taken from Basic Histology Text &
Atlas , 10th edition, L. Carlos Junquira MD,
Jose Carneiro MD, Robert O. Kelley PhD,
Lange Medical Books, Mc Graw-Hill , 2003.

The Corpus luteum

The wall of the follicle collapses into a folded
structure (characteristic for the corpus luteum).
Vascularization increases
Connective tissue network is formed.
Theca interna cells and granulosa cells triple in size
and start accumulating lutein within a few hours after
ovulation (granulosa lutein cells and theca lutein cells
and produce progesterone and oestrogens)
Hormone secretion in the corpus luteum ceases
within 14 days after ovulation if the oocyte is not
fertilised (the corpus luteum degenerates into a
corpus albicans - whitish scar tissue within the
ovaries).
Hormone secretion continues for 2-3 month after
ovulation if fertilisation occurs.

Low Magnification Ovary with a number of Corpus Luteum (CL)

CL

Arrow =
Secondary
Follicle

CL

CL
ERDS & LDL

CL

Human
Corpus
Luteum

ERDS & LDL

Corpus
luteum

Corpus Luteum

MedullaOvary &
CorpusLuteum

Corpus Luteum Corpus albicans

Low Magnification Corpus Albicans a

degenerated Corpus Luteum

ERDS & LDL

Oviduct
Functions : as a conduit for the
oocyte, from the ovaries to the
uterus.
Histologically :
the oviduct consists of :
a mucosa and a muscularis.
The peritoneal surface of the
oviduct is lined by a serosa and
subjacent connective tissue.

Oviduct
The mucosa

Is formed by a ciliated and secretory epithelium

resting on a very cellular lamina propria.
The number of ciliated cells and secretory cells
varies along the oviduct (see below).
Secretory activity varies during the menstrual
cycle, and resting secretory cells are also
referred to as peg-cells.
Some of the secreted substances are thought to
nourish the oocyte and the very early embryo.

The muscularis

Consists of an inner circular muscle layer and an

outer longitudinal layer.
An inner longitudinal layer is present in the isthmus
and the intramural part (see below) of the oviduct.
Peristaltic muscle action seems to be more important
for the transport of sperm and oocyte than the action
of the cilia.

Oviduct
Four subdivisions of the oviduct :
1. The infundibulum : funnel-shaped (up to 10 mm in
diameter) end of the oviduct.
Finger-like extensions of its margins, the fimbriae, are
closely applied to the ovary.
Ciliated cells are frequent. Their cilia beat in the
direction of
2. the ampulla of the oviduct.
Mucosal folds, or plicae, and secondary folds which arise
from the plicae divide the lumen of the ampulla into a
very complex shape.
Fertilization usually takes place in the ampulla.
3. The isthmus is the narrowest portion (2-3 mm in diameter)
of the parts of the oviduct located in the peritoneal cavity.
Mucosal folds are less complex and the muscularis is
thick. An inner, longitudinal layer of muscle is present in
the isthmus and the
4. Intramural part of the oviduct, which penetrates the wall
of the uterus.

Low Magnification The Ovary

ERDS & LDL

and the Oviduct (Fallopian Tube)

Uterine Tube

Three layers:
Mucosa
Muskularis
Serosa

Picture taken from Basic Histology

Text & Atlas , 10th edition, L.
Carlos Junquira MD, Jose
Carneiro MD, Robert O. Kelley
PhD, Lange Medical Books, Mc
Graw-Hill , 2003.

Wall of an oviduct
Highly folded
mucosa indicates
that this region is
close to ovary.
PT stain
Low magnification

Oviduct Epithelial
Ciliated cells
contribute to
movement of
oocyte or
conceptus to uterus
PT stain.
High magnification.

Oviduct

The Uterus

The uterus is divided into

1. Body (upper two-thirds) and
2. Cervix

The walls of the uterus are

composed of a
. Mucosal layer (the endometrium)
. A fibromuscular layer (the
myometrium).
. The peritoneal surface of the
uterus is covered by a serosa

Phases on Menstrual Cycle

UTERUS

The Uterus
Endometrium

Consists of a simple columnar epithelium

(ciliated cells and secretory cells) and an
underlying thick connective tissue stroma.
The mucosa is invaginated to form many
simple tubular uterine glands.
The glands extend through the entire
thickness of the stroma.
The stromal cells of the endometrium are
embedded in a network of reticular fibres.
The endometrium is subject to cyclic
changes that result in menstruation. Only
the mucosa of the body of the uterus
takes part in the menstrual cycle

The Uterus
Endometrium
The endometrium can be divided into two zones
based on their involvement in the changes
during the menstrual cycle: the basalis and
the functionalis.
The basalis is not sloughed off during
menstruation but functions as a regenerative
zone for the functionalis after its rejection.
The functionalis is the luminal part of the
endometrium. It is sloughed off during every
menstruation and it is the site of cyclic
changes in the endometrium. These cyclic
changes are divided into a number of phases:
proliferative (or follicular), secretory (or luteal),
and menstrual.

The Uterus

Myometrium
The muscle fibres of the uterus
form layers with preferred
orientations of fibres (actually 4),
but this is very difficult to see in
most preparations.
The muscular tissue hypertrophies
during pregnancy, and GAPjunctions between cells become
more frequent.

Straight uterine glands in deep endometrium

during proliferative phase. Smooth muscle of
myometrium is also seen. H&E stain. Medium
magnification

The surface epithelium & uterine glands are

embedded in a lamina propria made of very
loose connective tissue.
PT stain. Medium magnification.

Uterine glands during luteal phase

uterine glands become tortuous and their
lumen is filled with secretions. Some
edema is present in the connective tissue.
H&E stain. Medium magnification.
Inset: High magnification.

Reproductive Changes

Cervix

TRANTITIONAL EPITHELIUM (T zone)

GOES FROM SQUAMOUS (ectocervix)
TO SECRETING (UTERINE GLANDS)
COLUMNAR EPITHELIUM
(endocervix).
VISCOUS OF MUCUS GLANDS
CHANGES WITH MENSTRUAL CYCLE
MULTILAYERED:
MUCOSAL

FOLDS OF STRATIFIED
EPITH
NOT KERATINIZED BUT
KERATOHYALIN GRANULES
MAY BE VISIBLE
NO GLANDS BUT CELLS
ARE HIGH IN GLYCOGEN
MUCUS COMES FROM
CERVICAL GLANDS

Cervix in
Womans
Life

The cervix of a 14year-old sexually

active female.

Colpophotograph of the
cervix of a 14-year-old
nonsexually active
female

Cervix

Structure of the ectocervix:

CT=connective tissue, BM=basement
membrane, L1=basal cells (1 layer),
L2=parabasal cells (2 layers),
L3=intermediate cells (around 8 layers),
L4=superficial cells (5 or 6 layers) and
L5=exfoliating cells

Normal endocervix: epithelium

composed of one layer of mucin
secreting cells with few reserve
cells (arrow).

Ectocervix

Structure of the ectocervix - details of

basal, parabasal & intermediate layers:
connective tissue, basal cells (one layer),
parabasal cells (two layers), intermediate
cells (some layers) with inter-cellular
bridges. The N/C ratio of basal & parabasal
cells is high

Structure of the ectocervix :

details of the superficial layers :
superficial cells (5 or 6 layers). The
N/C ratio is very low and the axis of
cells is parallel to the basement
membrane

Transformation Zone

Transformation zone: normal

squamous epithelium (red star),
squamous metaplasia (green star) with
some remaining endocervical cells (blue
arrow)

Transformation zone: squamous

epithelium islet in the endocervix
area.
All cervix pictures downloaded from :
http://screening.iarc.fr/atlasglossdef.p
hp?key=Normal+endocervix&img

Cervix Cells &

paps smear

Different types of squamous cells - A: superficial cells

(arrows); B: intermediate cells; C: parabasal cells; D:
metaplastic cells. (obj. 20x)

HSIL. (obj. 20x)

There is a cervical
intraepithelial
neoplasia
(CIN) 3 lesion at (1),
and within the stroma
there are infiltrating
malignant cells (2)

Vagina
The vagina is a fibromuscular tube with a wall
consisting of three layers:
Mucosa
The stratified squamous epithelium (deep stratum basalis,
intermediate stratum spinosum, superficial layers of flat
eosinophilic cells which do contain keratin but which do not
normally form a true horny layer) rests on avery cellular
lamina propria (many leukocytes). Towards the muscularis
some vascular cavernous spaces may be seen (typical
erectile tissue).
Muscularis
Inner circular and outer longitudinal layers of smooth muscle
are present. Inferiorly, the striated, voluntary
bulbospongiosus muscle forms a sphincter around the
vagina.
Adventitia
The part of the adventitia bordering the muscularis is fairly
dense and contains many elastic fibres. Loose connective
tissue with a prominent venous plexus forms the outer part
of the adventitia.

Vagina

Stratified squamous epithelium of

vagina supported by a dense connective
tissue. The cytoplasm of these epithelial
cells is clear because of accumulated
glycogen.
PSH stain. Medium magnification.

Female Accessory Reproductive Glands Mammary Glands

Mammary glands modified glands of skin (resembles
that of sweat glands).
Compound branched alveolar glands, which consist of
15-25 lobes separated by dense interlobar connective
tissue and fat (Each lobe contains an individual gland)
The excretory duct of each lobe, also called lactiferous
duct, has its own opening on the nipple.
The lactiferous duct has a two layered epithelium basal cells are cuboidal whereas the superficial cells are
columnar.
Beneath the nipple, the dilated lactiferous duct forms a
lactiferous sinus , which functions as a reservoir for the
milk.
Branches of the lactiferous duct are lined with a simple
cuboidal epithelium.
The secretory units are alveoli, which are lined by a
cuboidal or columnar epithelium.
A layer of myoepithelial cells is always present between

Breast in Womans Life

Mammary Gland

normal
tdlu

Breast
Cancer

Pregnancy

Fungsi Plasenta
Kata

1.
2.
3.
4.
5.
Tahapan prelakunar
Pembelahan
Fertilisasi
lakunar
perkembangan
zygot
villi plasenta:
Tahapan
pembentukan

Animasi

TAMPILAN PLASENTA NORMAL

Placenta

Potongan Tali
Pusat Normal:
2 arteri & 1
Vena

Potongan T. Pusat
Abnormal: single
artery & single
vein

Umbilical Cord

Placenta
The placenta may be usefully
understood as a "parasite" feeding on
blood from the endometrium (Imagine
scooping out a portion of the
endometrium).
The resulting bowl will fill with blood
from broken vessels in the endometrial
stroma.
Now lay a cover over the bowl, and
imagine many "roots" extending down
from the cover into the blood-filled

Placenta

The cover is the chorionic plate of the placenta.

The "roots" are the chorionic villi.
Both the placenta and the chorionic villi are entirely fetal tissue
(orange in the diagram above).
"Anchoring villi" attach the placenta to the endometrium.
Smaller branching villi extend out into the intervillous space.
Fetal circulation passes down the umbilical cord, though vessels in
the villi, and back up the umbilical cord.
Maternal blood "spills" from open endometrial arteries (the spiral
arteries) into the intervillous space (pink in the diagram above), and
returns into endometrial veins.
The chorionic villi are surrounded and bathed by "lakes" of maternal
blood. Within the intervillous space, maternal blood is not contained by
blood vessels
The surface of the chorionic villi is an epithelial layer, the fetal
syncytiotrophoblast, which has the ability to grow invasively into the
maternal endometrium. The syncytiotrophoblast also has microvilli on
the surface for absorbing nutrients from maternal blood.
Beneath the syncytiotrophoblast (i.e., toward the core of the villus), is
the cytotrophoblast, a layer of cuboidal cells which eventually
disappear. (The cytotrophoblast also forms trophoblast columns,
masses of cells filling the ends of anchoring villi.)
Maternal endometrial stromal tissue adjacent to the placenta
differentiates into large decidual cells (so named because the outer
layer of the endometrium is shed at birth along with the placenta).
Decidual cells may intermix with fetal cells in the cytotrophoblast. The
boundary between maternal and fetal tissue is immunologically

Umbilical Cord
The umbilical cord is simply a conduit carrying
fetal blood between the fetus and the placenta.
It normally contains two arteries and one vein,
surrounded by extensive mesenchymal tissue
("Wharton's jelly").
Consists of so-called "mucous" or mesenchymal
connective tissue, also called Wharton's jelly
(widely scattered mesenchymal fibroblasts
within soft, jelly-like ground substance of
hyaluronic acid and chondroitin sulfate)
Surrounded by a thin stratified squamous
epithelium and including typically two arteries
and one vein. [The second vein in this image
presumably represents one portion of a double
U-shaped bend in this single vein.] The arteries
lack internal and external elastic layers.