Do I REALLY

Need Histology to
be A Doctor?
Female Reproductive System
Histology Department
 Introduction
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 FERTILIZATION
AND DEVELOPMENT
UTERUS
VAGINA
EXTERNAL PARTS :
OPENING OF THE VAGINA
LABIA (MAJORA & MINORA)
VESTIBULE DELIVER AND EXIT
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
development
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 &
flat follicular
Formed by:
an oocyte & cells
one layer
of cuboidal Picture taken
from Basic
granulosa cells Histology Text &
Atlas, 10th
edition, L. Carlos
Junquira MD,
Jose Carneiro
Pararosaniline MD, Robert O.
toluidine blue (PT)
stain. Kelley PhD,
Low magnification. Lange Medical
Books, Mc Graw-
Hill , 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.

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.

PT stain. High magnification.

 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 Theca Interna

Oocyte

ERDS
High Mag Graafian & LDL
Follicle
 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).
Given that atresia affects follicles at various stages of their
development it is obvious that the process may take on quite a
variety of histological appearances
Characteristic of FOLLICLE ATRESIA
1. Loss of cells of corona radiata
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
CL

Arrow =
Secondary CL CL
Follicle

ERDS & LDL

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

Germ Cell Tumor of Ovary

Teeth and a portion of jaw in a

benign cystic teratoma
Components of benign cystic teratoma.:
Respiratory epithelium and underlying
cartilage
 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.
The mucosa is smooth, and the inner diameter of the duct is very
small.
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.

Oviduct Epithelial
Ciliated cells
Wall of an oviduct contribute to
movement of
Highly folded oocyte or
mucosa indicates conceptus to uterus
that this region is PT stain.
close to ovary. High magnification.
PT stain
Low 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 GAP-junctions 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
 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
Cervix GLYCOGEN
MUCUS COMES FROM CERVICAL
GLANDS
MUSCULARIS-SMOOTH MUSCLE
ADVENTITIAL
 Cervix in
Womans Life
 The cervix of a 14-year-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
a very 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 the
epithelium and the basement membrane of the branches of the
lactiferous duct and the alveoli.
Breast in Womans Life
Mammary Gland
 Breast Cancer
normal tdlu
Pregnancy
Fungsi Plasenta
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 hollow (the roots can absorb oxygen
and nutrients from the blood in which they are
bathed).
 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
interesting.
Complete Hydatidiform
Mole
 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.