Histology of Female

Reproductive System
Histology Department
Fakultas Kedokteran
Universitas Sumatera Utara 2020
ERDS - LDL
 Female Reproductive System
Female reproductive system comprises of the following
organs:
Ovaries
Oviducts
Uterus
Vagina
External Genitalia

Mammary Gland is a skin appendix (Sweat Gland

Modified) but due to its close relation to reproductive
system explains here
 Ovary
Ovaries are small almond shaped organs lying in pelvic
cavities
The surface epithelium is simple cuboidal and known as
germinal epithelium
 Tunica albuginea is a dense irregular connective tissue that
is directly beneath epithelium
The ovary can be divided into two components: cortex and
medulla
Hilum is the route whereby vessels and nerves enter and
leave the ovary
Medulla is the core of ovary contains loose connective
tissue and vessels
Remnants of Wollfian ducts persists from embryonic period
and are irregular tubules lined by a cuboidal epithelium
 Ovary
Hilus cells are identical to Leydig cells, and may contain
Reinke’s crystalloids
Small clumps of hilus cells are often found near blood
vessels
Medulla contains stromal cells identical to those which
are in the cortex
Cortex has two components a stroma and structures
that producing gametes
Cortical stroma has closely packed spindle shaped
fibroblast-like cells which are arranged in a whorled
pattern
Collagen fibers between stromal cells are prominent in
outer cortex and with time the amount of collagen will
 Ovary
 Stroma provides structural support, forms theca
interna and externa around follicles, and
secretes steroid hormone
 There is three types of stromal steroid secreting
cells:
I. Scattered luteinized stromal cells which are
numerous during pregnancy
II. Stromal cells that form theca layers
III. Enzymically active stromal cells (EASC)which
are numerous in postmenopausal women and
secret testosterone
 Ovarian Follicles
 Ovarian follicles located in cortex
and surrounded by stromal cells
 A follicle consists of an oocyte
surrounded by one or more layers
of follicular cells
 2 ovaries of young adult female
have about 400,000 follicles;
most of them will degenerate
(atresia)
 About 450 follicles will cycle to
ovulation in lifetime
 According to
Types of Ovarian Follicles morphological
characteristic follicles
can be categorized into:
 Primordial Follicles
 Growing Follicles
 Unilaminar primary
follicles
 Multilaminar primary
follicles
 Secondary follicles
 Mature Follicles
(Tertiary or Graafian
Follicles)
Primordial Follicle
• Primordial follicles contain a primary oocyte
that entered the prophase of first mitotic
division
• Primary oocyte surrounded with one layer of
flattened follicular cells which are separated by
a basal lamina from the stroma
• Many of them degenerate during lifetime
• Most numerous in fetus (several million)
• One million at birth
• At the onset of the buberty their number
reduced to about a quarter of a million
• Oocyte about 25 µm diameter
• Euchromatic nucleus, large nucleolus
 Primary Follicles
 Oocyte diameter increases to 100 to 150 µm
 Nucleus enlarges and called germinal
vesicle(GV)
 Organelles increase in number and amount
(mitochondria, several golgi complexes,
RER, free ribosomes)
 Follicular cells become cuboidal
 Unilaminar primary follicle has one layer of
cuboidal follicular cells
 Multilaminar primary follicle has several
layers of follicular (granulosa) cells
Unilaminar
 Zona pellucida secreted by oocyte and is
composed of 3 glycoproteins ZP1, ZP2, ZP3
forms just outside oocyte membrane, thick
basal lamina
 Follicle cell filopodia extend into Zona
pellucida as do oocyte microvilli, joined by
gap junctions
 Stromal cells differentiate into theca folliculi
that has a theca interna and theca externa
 A thickened basal lamina separated theca
interna from granulosa cells
Multilaminar
Theca Interna & Theca Externa
Theca Interna
 Cells are more cuboidal with round nuclei
 steroid producing cell features
 SER, mitochondria with tubular cristae and lipid droplets
 produce androstenedione which is converted to
estradiol by granulosa cells
 highly vascularized
Theca externa
 Composed of connective tissue and stromal cells with
vessels forming a plexus
 cells are flattened
 Secondary Follicles
 Granulosa and theca cells increase in
number
 Fluid-filled spaces in granulosa layer fuse
to form the antrum that become filled with
liquor folliculi
 This fluid is an exudates of plasma and
produced by granulosa cells. It contains
GAGs, proteoglycans, steroid binding
protein, steroids and some hormones.
 Cumulus oophorus is a small group of
granulosa cells that surround primary
oocyte and project into antrum
 A single layer of granulosa cells that
immediately surround the primary oocyte
is known as corona radiata
 Most of follicle at this stage become atretic
 Some granulosa cells of atretic follicles do
not degenerate and form interstitial glands
which secret androgens
Mature (Graafian)
Follicles
Mature follicle develops due
to continued proliferation of
granulosa cells and production
of more liquor folliculi which
undergo ovulation
By the time of ovulation it
may be over 2.5 cm in
diameter
Bulge from ovary surface
Because of continued
formation of liquor folliculi
cumulus oophorus detaches
and float freely in liquor
folliculi
Oocyte Meiotic Divisions
First meiotic
division occurs just
prior to ovulation
under the influence of
meiosis inducing
factor
Second meiotic
division then begins
and stops at metaphase
Second meiotic
division is completed
after fertilization
 Ovulation
Fluid pressure builds up until follicle ruptures due to
formation of proteoglycans and hyaluronic acid and
attraction of water
Before ovulation the surface of ovary loses its blood
supply just where the follicle pressing it and known as
stigma
Perifollicular connective tissue broken down by
proteases
Ovum (Secondary oocyte) is drawn into open end of
oviduct (fallopian tube)
Ovum remains viable about 24 hours after ovulation
Remnants of graafian follicle are converted to corpus
hemorrhagicum
Corpus
Hemorrhagicum
• Following ovulation the
remainder of follicle collapses
and some ruptured blood vessels
leak into follicular cavity and
forming a clot that is known as
corpus hemorrhagicum
Corpus Luteum
After removing the clot by phagocytes a
temporary hormone secreting structure
formed by granulosa cells and theca
interna cells known as corpus luteum
Granulosa cells hypertrophy into large
pale staining granulosa-lutein cells with
organelles necessary for steroid
production
They constitute about 80% of the cells
of corpus luteum
These cells produce progesterone and
convert androgen produced by theca-
lutein cells into estrogens
Corpus Luteum
Theca interna cells form theca-
lutein cells which are smaller and
darker staining than granulosa-lutein
cells
Located in folds of cells in
perimeter of corpus luteum form
about 20% of cells population and are
highly vascularized
Produce estrogen, progesterone and
androgens
If pregnancy does not occur corpus
luteum of mensturation survives only
10-14 days
In pregnancy it enlarges greatly due
to HCG and lasts 6 months and called
corpus luteum of pregnancy
Corpus luteum of pregnancy grows
to a 5 cm diameter structure
 Corpus Albicans
When the corpus luteum
degenerate it is invaded by
fibroblasts which manufacture
collagen type I and form a fibrous
structure known as corpus albicans
Large ones form after pregnancy
and smaller ones after each
ovulation
On the surface of ovary remnants
of corpus albicans is visible as a
scar
 Oviduct
Uterine tube is a muscular tube, 12 cm
long
It is the site of fertilization
Upper end opens into peritoneal cavity
near ovary
Lower end passes through the uterus
wall
Oviduct has 4 segments
intramural part in uterine wall
isthmus is adjacent to uterine wall
ampulla is dilated part
infundibulum is funnel-shaped part
near ovary with fimbriae
 Oviduct
Mucosa has many longitudinal folds which
are pronounced in the ampulla
Mucosa has a simple columnar epithelium
consist of ciliated cell and nonciliated peg
cell
Ciliated cells are numerous near ovarian end
of the tube
Peg cells are secretory cells that produce a
watery tubal fluid contains normal serum
proteins, chloride and potassium ions
Cilia near ovary beat toward uterus but cilia
near uterus beat toward ovary
Lamina propria composed of loose
connective tissue
Muscularis consists of poorly defined
Inner circular layer and outer
longitudinal layer of smooth muscle
cells
Muscularis peristaltic movements
with the beating of the cilia of
epithelium help to propel oocyte to the
uterus
Serosa is a connective tissue layer
lined by a simple squamous epithelium
contains blood vessels, and nerves
Oviduct
 Uterus
Uterus is a pear-shaped structure attached to
oviducts at upper end and to vagina at lower
end
Uterus is divided into three regions:
Body
Fundus
Cervix
Wall of body and fundus has 3 layers
• Endometrium
• Myometrium
• Adventitia/Serosa
Anterior portion of body covered by adventitia
which is composed of areolar connective tissue
 The remaining portion of uterus covered by
serosa composed of a layer of simple squamous
cells (mesothelium) resting on an areolar
connective tissue
 Myometrium
Myometrium is the thickest layer and composed of four
poorly defined layers of smooth muscle separated by
connective tissue
Inner and outer layers are mostly longitudinal in orientation
Middle layers are highly vascularized and consist of mostly
circularly arranged bundle of smooth muscle cells
Arcuate arteries located in this layers and is known as
Stratum Vasculare
Middle layers thicken during pregnancy with more and large
smooth muscle cells (hyperplasia and hypertrophy) and
increased collagen fibers
Myometrium is estrogen dependent in absent of estrogen
smooth muscle cell atrophies and some of the begin to
apoptosis
 Endometrium
Endometrium is mucosal lining of
uterus composed of a simple columnar
epithelium
Epithelium has ciliated columnar cells
and secretory columnar cells
Lamina propria composed of dense
irregular connective tissue and vessels
supports epithelium and houses simple
tubular glands
The glands have not ciliated cells
Endometrium has 2 zones
Functional layer
Basal layer
 Endometrial Layers
Functional layer is a thick superficial
layer sloughed off during menstruation
and replaced during each menstrual cycle
Functional layer vascularized by coiled
helical arteries that originate from
arcuate arteries in stratum vasculare
Basal layer is a deep narrow layer
retained after menstruation whose glands
epithelium and connective tissue element
regenerate functional layer
Basal layer supplied by short straight
arteries which originate from arcuate
arteries in stratum vasculare
 Menstrual Cycle
Estrogen and progesterone from ovary stimulate changes in
the endometrium
The average menstrual cycle is 28 day
Begins age is about 12-15 y/o and ends age is about 45-50 y/o
The menstrual cycle has 3 main phases
Menstrual phase: days 1-4
Proliferative (follicular) phase: days 5-14
Ovulation around day 14
Secretory (luteal) phase: days 15-28
 Proliferative (Follicular) Phase
 Days 5-14 leading up to ovulation
 Estrogen produced by theca cells of
ovarian follicle
 Cells of gland bases proliferate
forming simple columnar epithelium
and tubular glands of endometrium
 Connective tissue cells proliferate in
lamina propria
 Coiled arteries grow into
regenerated lamina propria
 Functionalis of endometrium
become 2-3 mm in thickness
 glands have a straight tubes with
narrow lumens but their cells
accumulate glycogen
 At the day 14 the functional layer
has been fully restored
 Secretory (Luteal) Phase
 Begins after ovulation, days
15-28
 Corpus luteum forms and
produces progesterone
 Glands develop further,
become highly coiled,
branched and begin to
secrete
 Coiled arteries also attain
full development
 Endometrium reaches 5 mm
in thickness due to edema
and accumulated glycogen
secretions of the glands
 Menstrual Phase
 If fertilization does not take place the corpus
luteum stops secreting hormones after about
14 days
 Progesterone and estrogen decrease causing
coiled arteries to intermittently constrict
cutting off blood flow to the functional layer
of endometrium
 Endometrial cells die and the functional layer
is sloughed off
 Then coiled arteries dilate once again, because
they are weakened they rupture
 The disgorged blood removes patches of the
functional layer as menses
 Vessels distal to constrictions are shed with
the functional layer causing some bleeding
 About 35ml blood loss occur during
mensturation
 Uterine Cervix
 Cervix is the lower part of uterus that protrude into vagina
 It is lined by mucous secreting simple columnar epithelium
 Part of cervix in upper vagina has stratified squamous
nonkeratinized epithelium
 Lamina propria composed of mostly dense connective tissue
and many elastic fibers and a few smooth muscle cells
 Mucosa do not slough off during menstruation
 Cervical mucosa contains branched cervical glands
 At time of ovulation cervical glands secrete a serous fluid
 At other time the secretion become viscous and during
pregnancy forming a plug
 Softening of cervix during parturition is due to lysis of collagen
 Vagina
• A thick stratified squamous nonkeratinized epithelium
lines the vaginal mucosa
• Estrogen stimulates epithelium to synthesize glycogen
• Mucosa has not glands but increment of fluid during
sexual arousal is due to transudate from vessels of lamina
propria and secretion of cervical glands
• Underlying lamina propria composed of loose connective
tissue that highly vascularized with many elastic fibers
• Muscular layer of circular and a prominent longitudinal
smooth muscle fibers
• Adventitia of dense irregular connective tissue with
elastic fibers, many vessels and vast venous plexus and
nerves
 VAGINA LABIA MINORUM

MUCOSA

STRATIFIED SQUAMOUS EPITHELIUM

LAMINA PROPRIA

---------------- no glands ----------------

MUSCULARIS
INNER CIRCULAR
OUTER LONGITUDINAL

ADVENTITIA
 Female Urethra
§Female urethra is about 5 cm in length
§It is lined by transitional epithelium near bladder and stratified
squamous nonkeratinized in reminder portion
§Patches of pseudostratified columnar is interspersed
§Lamina propria is a fibroelastic connective tissue
§Mucous secreting glands of Littre are numerous along its length
§Muscular layers is composed of an outer circular and an inner
longitudinal smooth muscle fibers
§When urethra pierce urogenital diaphragm a sphincter of
skeletal muscle surrounds it
 External Genitalia(Vulva)
External genitalia is consists of mons pubis, labia majora,
labia minora, clitoris, Bartholin’s glands, minor vestibular
glands, and hymen
Mons pubis is the are overlying symphysis pubis covered by
skin that underneath it is a pad of fat
Labia majora are skin folds with an adipose core and a thin
layer of smooth muscle
skin with coarse hair on their external surface, sweat and
sebaceous glands, many nerve fibers
Labia minora are folds of skin without hair and with core of
spongy connective tissue with elastic fibers
skin with sebaceous and sweat glands, and many nerve fibers
 External Genitalia
Clitoris is embryonic homologue of penis
contains 2 erectile tissue bodies
covered by stratified squamous epithelium
heavily innervated
Bartholin’s glands are mucous secreting glands with
ducts opening into the vestibule of vagina
Minor vestibular glands are also opened into vestibule
Hymen is a thin fold of epithelially enclosed
fibrovascular connective tissue that narrow the orifice of
vagina in virgin
 Mammary Glands
Mammary gland consists of 15-25 lobes of
compund tubuloacinar glands similar to apocrine
sweat glands
Glands secrete by apocrine mechanism (lipids) and
exocytosis (proteins)
Each lobe surrounded by dense irregular
connective tissue and adipose tissue
Connective tissue surrounding acini has many
plasma cells and lymphocytes, sources of milk
immunoglobulins
Each lobe has its own duct leading into lactiferous
ducts of nipple
Interlobular ducts have simple cuboidal epithelium
surrounded by myoepithelial cells
Lactiferous sinuses lined by stratified squamous
epithelium that changes to stratified columnar or
cuboidal deeper in lactiferous ducts
Glandular cells proliferate during pregnancy
 Areola & Nipple
• Areola is a circular highly pigmented skin around
nipple; color darkens during pregnancy due to
increased melanin production by melanocytes
• Areola contains sweat and sebaceous glands and also
areolar glands of Montgomery that resemble both
sweat and mammary glands
• Nipple is a protuberance at the center of areola that is
covered by stratified squamous keratinized epithelium
• Terminal portion of lactiferous ducts end at nipple
• The core of nipple is composed of dense collagenous
CT with abundant elastic fibers connected to skin
• Abundant smooth muscle fibers arrange in circular
way around nipple and in longitudinal way along long
axis of the nipple
PLACENTA
After 20 days the bundle of cells had changed into
an early kind of body, an embryo.
• By one month you were the size of an apple seed and
needed more food to grow so the cell clump made you a
food factory - the placenta.  
Fetal Side Maternal Side
Fetal Side
Villi generally cut in cross-section showing trophoblastic shell
with mesenchyme core. Shell (dark border) consists of an outer
variable thickness of syncitiotrophoblasts with and inner layer of
cytotrophoblast cells.
Core (pale interior, space is artefact) consists of mesenchymal
cells forming an undifferentiated connective tissue with fetal
blood vessels coursing through this region.
Note region closest to maternal side shows large
syncitiotrophoblast clumps (dark purple regions).
Maternal Side
Notice the decidual reaction glycogen deposits (bright
magenta/red) close maternal surface. on right of image lumenal
space of endometrial glands with precipitated contents.
Compare the thickness of the endometrial layer with that seen
during the menstrual cycle.
Section through
the junction
between the
fetal and
maternal
portions of the
placenta. Note
the chorionic
villi and the
highly vascular
stratum basale
into which the
villi anchor

Maternal Side Fetal Side