• It undergoes marked changes at the

onset of puberty
 MENARCHE: first sign of Puberty in
females
• It exhibits monthly menstrual cycles and
menses from puberty until the end of the
reproductive years
 MENOPAUSE
 OVARIES
covered by a simple cuboidal epithelium
called the germinal epithelium.
TUNICA ALBUGINEA: capsule deep to the
germinal epithelium
composed of a dense, irregular collagenous
connective tissue.
Each ovary is subdivided into a cortex and a
medulla (both are not sharply delineated)
 OVARIAN CORTEX
• consists of ovarian follicles in various stages of
development embedded in a connective tissue
stroma containing hormone sensitive cells
The Follicles Journey

Primordial Follicle Growing Follicles

- Primary Follicle
- Primary Oocyte Corpus Luteum
- Secondary Antral
- Follicle cells - Graafian follicle

Atretic follicle Corpus Albicans

 OVARIAN FOLLICLES
a. Primordial follicles are composed of a primary
oocyte enveloped by a single layer of flat follicular
cells
 Primary Oocytes
 display a prominent,
acentric, vesicular-appearing
nucleus possessing a single
nucleolus.
become arrested in
prophase of meiosis I by
paracrine factors produced
by the follicular cells during
fetal life and remain in this
stage until ovulation
(perhaps for years).
 Primordial Follicles – Follicular cells
• are attached to one another by desmosomes
• are separated from the surrounding stroma by
a basal lamina.
Growing Follicle – Primary Follicle
• not dependent on follicle-stimulating hormone
(FSH) for their development.
• They possess an amorphous layer (zona pellucida)
surrounding and produced by the primary oocyte
• a basal lamina is present at the interface of the
follicular cells with the stroma.
UNILAMINAR PRIMARY FOLLICLES
• Unilaminar primary follicles - develop
from primordial follicles.
- are composed of a single layer of cuboidal
follicular cells surrounding the primary oocyte
 MULTILAMINAR PRIMARY FOLLICLES
o develop from unilaminar follicles by proliferation
of follicular cells.
o proliferate because of activin, a product of the
primary oocyte.
o consist of several layers of follicular cells;
o these follicular cells are now also known as granulosa
cells.
o are circumscribed by two layers of stromal cells:
o an inner cellular layer (theca interna)
o an outer fibrous layer (theca externa)
• The theca interna is separated from the granulosa
cells by a basal lamina.
• Cells of the theca interna manufacture
androstenedione (male sex hormone) and express
luteinizing hormone (LH) receptors on their cell
membranes.
SECONDARY ANTRAL FOLLICLES
• established when fluid (liquor
folliculi, an exudate of plasma
containing various hormones,
such as activin, estradiol,
follistatin, inhibin, and
progesterone) begins to
accumulate in the spaces
between granulosa cells.
• The fluid-filled spaces will
begin to coalesce, eventually
to form a single large cavity
called an ANTRUM.

• dependent on FSH.
 Mature (Graafian) Follicle
• The dominant graafian follicle is the one follicle among
the secondary follicles that will ovulate.
• It is FSH independent and manufactures the hormone
INHIBIN that shuts off FSH release by the basophils of
the anterior pituitary, causing atresia of the other
developing follicles (secondary and nondominant
graafian follicles).
• It measures approximately 2.5 cm in diameter and is
evident as a large bulge on the surface of the ovary.
 MATURE GRAAFIAN FOLLICLE
• The primary oocyte is positioned
off center on a small mound of
granulosa cells (cumulus
oophorus) that projects into the
liquor folliculi-containing antrum
of the follicle.
• Granulosa cells surround the
zona pellucida.
 Those contacting the zona
pellucida are known as the corona
radiata.
antrum,
Other granulosa cells line the
forming the membrana
granulosa.
 OVULATION
• Ovulation also occurs in response to the LH surge.
• The secondary oocyte and its corona radiata cells leave the ruptured
follicle at the ovarian surface to enter the fimbriated end of the
oviduct.

The corpus
hemorrhagicus is
formed from the
remnants of the
graafian follicle.
 CORPUS LUTEUM
• The corpus luteum is formed from the corpus
hemorrhagicus.
• It is composed of granulosa lutein cells (modified
granulosa cells) and theca lutein cells (modified
theca interna cells).
• The formation is dependent on LH.
CORPUS LUTEUM
 CORPUS LUTEUM
Granulosa lutein cells - are large (30 um in
diameter), pale cells - They are derived from
cells of the membrana granulosa.
 CORPUS LUTEUM
• Granulosa lutein cells manufacture most of
the body’s progesterone and convert
androgens formed by the theca lutein cells
into estrogens.
 CORPUS LUTEUM
Theca lutein cells
These small (15 um in diameter) cells are
concentrated mainly along the periphery of the corpus
luteum.
They are derived from cells of the theca interna.
Theca lutein cells manufacture progesterone and
androgens and small amounts of estrogen.
 CORPUS ALBICANS
• remnant of the degenerated corpus luteum
• Its formation is due to the hypoxic conditions present
in the corpus luteum as fibroblasts manufacture an
overabundance of collagen.
• The fibrotic event elicits the arrival of T cells that
release interferon-y, a chemoattractant for
macrophages.
• These cells release tumor necrosis factor a, a cytokine
that drives both granulosa lutein and theca lutein cells
into apoptosis.
• As the cell death and fibrosis progresses, the corpus
albicans contracts and becomes a small scar on the
surface of the ovary.
 Prominent in menopause

CORPORA ALBICANTIA
 ATRETIC FOLLICLES
• follicles (in various stages of maturation) that are
undergoing degeneration.
• They are commonly present in the ovary; after a
dominant graafian follicle ovulates, the remaining
graafian and secondary follicles degenerate.
• They often show pyknotic changes in the nuclei of
the granulosa cells and other degenerative
changes.
OVARIAN MEDULLA
 OVARIAN MEDULLA
• contains large blood vessels, lymphatic
vessels, and nerve fibers in a loose connective
tissue stroma.
• They also possess a small number of estrogen-
secreting interstitial cells and a few androgen-
secreting hilus cells.
CLINICAL CORRELATION:
MUCINOUS AND SEROUS
CYSTADENOMA
Normal Ovary in Cross Section:
Uniloculated or
Multiloculated
filled with Slid
Papillary
Growth
 Diagnosis:
• Benign: Mucinous Cystadenoma vs.
Serous Cystadenoma (Simple
Columnar epith)
• Cancer: Serous
Cystadenocarcinoma vs. Serous
Cystadenocarcinoma ( Simple
Cuboidal to flattened cells)
CLINICAL CORRELATION:
MATURE CYSTIC TERATOMA
Teratomas are germ cell tumors that fall into three
groups: mature, monodermal, and immature.
Mature teratomas are benign (although
occasionally they may become malignant) and
are usually present in young women.
These are cysts with walls that frequently contain
hair and other epidermal structures such as
sebaceous glands, as well as bone, tooth, and
cartilage fragments.•hCG and/or AFP in 50% of cases.
• Mature cystic teratoma (dermoid cyst)Germ cell
tumor, most common ovarian tumor in women
20–30 years old.
• Can contain elements from all 3 germ layers;
teeth, hair, sebum are common components.
• Can present with pain 2° to ovarian enlargement
or torsion.
• Can also contain functional thyroid tissue and
present as hyperthyroidism (struma ovarii).
 OVIDUCTS
• subdivided into four regions:
the infundibulum, which has a fimbriated end;
the ampulla, which is the most common site of
fertilization
the isthmus
the intramural portion, which traverses the wall
of the uterus.
• The wall of each oviduct consists of a mucosa,
muscularis, and serosa.
• MUCOSA: has extensive longitudinal folds
in the infundibulum.
– The degree of folding progressively
decreases in the remaining three regions of
the oviduct.
o The epithelium is simple columnar and consists of
peg cells and ciliated cells.
a. Peg cells - secrete a nutrient-rich medium
that nourishes the spermatozoa (and preimplantation
embryo), as well as cytokines that aid in the
capacitation of spermatozoa.
b. Ciliated cells - cilia beat mostly toward
the lumen of the uterus. - aids in the
transport of the developing embryo to the
uterus.
Lamina propria: consists of loose connective
tissue containing reticular fibers, fibroblasts,
mast cells, and lymphoid cells.
 MUSCULARIS
o The muscularis is composed of an ill-defined
inner circular and an outer longitudinal layer
of smooth muscle. ICOL
o By contracting rhythmically, the muscularis
probably assists in moving the embryo toward
the uterus.
 SEROSA
The serosa, which is composed of a simple
squamous epithelium overlying a thin
connective tissue layer, covers the outer
surface of the oviduct.
 UTERUS
The uterus has three regions:
 the fundus
 body (corpus)
 cervix
UTERINE WALL
• consists of the:
 endometrium
myometrium, and
adventitia (or serosa)
 ENDOMETRIUM
•composed of an epithelial lining and a gland-rich
connective tissue stroma, undergoes hormone-
modulated cyclic alterations during the menstrual cycle.
It is lined by a simple columnar epithelium containing
secretory and ciliated cells.
Its stroma resembles mesenchymal connective tissue,
with stellate cells and an abundance of reticular fibers.
Macrophages and leukocytes are also present.
endometrium.
The stroma houses the simple tubular glands of the
PROLIFERATIVE PHASE SECRETORY PHASE
ENDOMETRIUM ENDOMETRIUM
PROLIFERATIVE PHASE SECRETORY PHASE
ENDOMETRIUM ENDOMETRIUM
 LAYERS OF ENDOMETRIUM
The functional layer (functionalis) is
the thick superficial layer of the
endometrium that is sloughed and
reestablished monthly as a result of
hormonal changes during the
menstrual cycle.
The basal layer (basalis) is the deeper
layer of the endometrium that is
preserved during menstruation.
It has endometrial glands, which have
basal cells that provide a source for
reepithelialization of the endometrium
after the functional layer is shed.
 ENDOMETRIAL VASCULAR SUPPLY
consists of two types of
arteries derived from vessels
in the stratum vasculare of the
myometrium.
(1) Coiled arteries extend into
the functional layer and
undergo pronounced changes
during various stages of the
menstrual cycle. (2) Straight
arteries do not undergo cyclic
changes and terminate in the
basal layer.
 CASE # 02
A 32 year old female who had been married for
the past 4 years consulted for gynecologist for
infertility. She claimed to have severe
dysmenorrhea in the past few month and
dyspareunia.
 CASE # 02: GROSS
• The left ovary measures 25 x 15 mm and is
grossly unremarkable.
 CASE # 02: MICROSCOPIC
• Section shows ovarian tissue exhibiting a small
cystic structure lined by endometrial
epithelium and partly filled with blood.
 ENDOMETRIOSIS
• Endometriosis is a condition in which
the pelvic peritoneal cavity contains
uterine endometrial tissue.
 MYOMETRIUM
• The myometrium is the thick smooth muscle tunic of
the uterus.
• It is composed of inner and outer longitudinal layers
and a thick middle circular layer. The circular layer is
richly vascularized and is often referred to as the
stratum vasculare.
• The myometrium
thickens during
pregnancy because of
the hypertrophy and
hyperplasia of
individual smooth
muscle cells.
• Near the end of
pregnancy, the
myometrium develops
many gap junctions
between its smooth
muscle cells -
coordinate contraction
of the muscle cells
during parturition
• At parturition, the myometrium undergoes
powerful contractions triggered by the
hormone oxytocin and by prostaglandins
(both of which are increased at term).
• After parturition, the myometrium shrinks
because many of the smooth muscle cells
become deprived of estrogen and, therefore,
undergo apoptosis.
 SEROSA AND ADVENTITIA
• Serosa is present over surfaces of the uterus
bulging into the peritoneal cavity.
• Adventitia is present along the
retroperitoneal surfaces of the uterus.
 CASE # 03
A 34 year old female consulted for gynecologist
with complaints of dyspareunia and pelvic pain
especially during the premenstrual period. She
claims that her menstrual bleeding is profuse
consuming 7-8 napkins per day and lasts for 5-7
days.
 CASE # 03: GROSS
• The uterus is enlarged weighing 190 grams
and measuring 90 x 50 x 35 mm. The
endometrium and myometrium measure 1
mm and 34 mm in thickness respectively. Cut
surface shows numerous small cysts within
the thickened myometrium.
 CASE # 03: MICROSCOPIC
Sections shows myometrial tissue embedded
within which are irregular nests of endometrial
stroma and endometrial glands. These
endometrial tissue are seen about two high
power fields below the basalis.
ADENOMYOSIS
 ADENOMYOSIS
• Presence of endometrial Tissue within the Uterine
wall (myometrium)
• Remains in continuity with the endometrium
(downgrowth of the endometrial tissue into and
between the smooth muscle fascicles of the
myometrium)
• Mx: Irregular nests of endometrial stroma with or
without glands are arranged within the myometrium
separated from the basalis at least 2-3 mm
• Sx: Menorrmetorrhagia (irregular and heavy
menses), colicky dymenorrhea, dyspareunia, pelvic
pain
• The cervix does not participate in menstruation,
but its secretions change during various stages of
the menstrual cycle.
• The cervical wall is composed mainly of dense
collagenous connective tissue interspersed with
numerous elastic fibers and a few smooth muscle
cells.
• The cervix has simple
columnar (mucus-
secreting) epithelium
except for the inferior
portion (continuous
with the lining of the
vagina), which is
covered by a stratified
squamous
nonkeratinized
epithelium (
exocervix)
SQUAMO-COLUMNAR JUNCTION:

ECTOCERVIX ENDOCERVIX
 Changes in the Cervix:
• Branched cervical glands secrete a serous fluid
near the time of ovulation that facilitates the entry
of spermatozoa into the uterine lumen.
• During pregnancy, cervical glands produce a thick,
viscous secretion that hinders the entry of
spermatozoa (and microorganisms) into the
uterus.
• Prior to parturition, the cervix dilates and softens
as a result of the lysis of the collagen fiber bundles
in response to the hormone relaxin.
PAP SMEAR
 Carcinoma of the cervix
o originates from stratified squamous
nonkeratinized epithelial cells.
o It may be contained within the epithelium and
not invade the underlying stroma (carcinoma in
situ), or it may penetrate the basal lamina and
metastasize to other parts of the body (invasive
carcinoma).
o It occurs at a relatively high frequency but may be
cured by surgery if discovered early (by Pap
smear), before it becomes invasive.
SQUAMOUS CARCINOMA OF THE
CERVIX
 CASE # 07
• A 35 year old sexually active female
complained of several warty lesions on her
vulva. She revealed that her husband had
similar lesions on his penis as well.
 CASE # 07: MICROSCOPIC
Shows polypoid tissue lined by markedly
thickened stratified squamous epithelium
exhibiting papillomatous and prominent
acanthosis.
The cells of the upper portion of the epithelium
have perinuclear vacuolization and round
hyperchromatic nuclei.
Increase in mitosis is observed.
The subepithelial tissue shows dilated blood
vessels and mild lymphocytic inflitrates.
DIAGNOSIS:
CONDYLOMA ACUMINATUM
 CONDYLOMA ACUMINATUM
• Benign Genital Warts caused by low oncogenic risk
HPVs (mainly types 6 and 11)
• May be solitary but more frequently multifocal
• May involve Vulvar, Perineal and Perianal regions,
Vagina, less commonly the cervix
• Hx: Papillary, exophytic, treelike cores of stroma
covered by thickened squamous epithelium
• Surface epithelium shows characteristic viral cytopathic
changes: koilocytic atypia
– Nuclear enlargement, hyperchromasia and a cytoplasmic
perinuclear halo
• Not Precancerous Lesions
• HPV—warts (1, 2, 6, 11), CIN, cervical cancer (16, 18) vaccine
available.
• Squamocolumnar junction (most common area for cervical cancer).
Koilocytes (HPV: predisposes to cervical cancer)Dysplastic squamous
cervical cells with nuclear enlargement and hyperchromasia
 FERTILIZATION
• Fertilization usually takes place within the ampulla of the
oviduct.
• It occurs when a spermatozoon penetrates the corona radiata
and the zona pellucida and pierces the plasma membrane of a
secondary oocyte.
• It triggers the resumption and completion of the second
meiotic division with the formation of two new cells, the
ovum and the second polar body.
• It is completed when the male haploid (n) pronucleus (derived
from the spermatozoon) and the female haploid (n)
pronucleus (derived from the ovum) fuse, forming a diploid
(2n) cell known as a zygote.
IMPLANTATION
ZYGOTE
Mitosis
MORULA (Multicellular
Structure)
3 days
Enters the Oviduct and to
the Uterus

CONCEPTUS (fluid
filled cavity)
 IMPLANTATION
• The blastocyst implants in the endometrium
of the uterus and is surrounded by an inner
cellular layer (cytotrophoblast) and an outer
multinucleated layer (syncytiotrophoblasts)

• The syncytiotrophoblast further invades the

endometrium in the wall of the uterus by the
sixth day after fertilization.
• Formation of the placenta then begins.
 CASE # 04
A 37 year old female was admitted to the
hospital for severe abdominal pain and loss of
consciousness. Ultrasound showed a mass in the
right lower abdomen. Exploratory laparotomy
revealed blood in the abdominal cavity. The
right fallopian tube was enlarged and covered
with blood clot.
 CASE # 04 : GROSS
• The fallopian tube measures 60 mm in length and
varies from 5 to 30 mm in diameter. On section, the
lumen is distended with soft grayish-brown material.
A point of rupture is noted in one area and is covered
with blood clot.
 CASE # 04: MICROSCOPIC
• Section shows the lumen of the tube to be
filled with blood clot. In one area, several
chorionic villi are seen lined by two layers of
the trophoblastic cells and supported by a
poorly vascularized stroma. The wall of the
tube is thickened and ruptured in one area.
Around the rupture are extravasated red
blood cells.
DIAGNOSIS:
ECTOPIC PREGNANCY
 ECTOPIC PREGNANCY
• Refers to implantation of the fetus in the site
other than the normal intrauterine location
• The most common site is the Extrauterine
Fallopian tube (90% of cases)
• Tubal Pregnancy is the MOST COMMON CAUSE
OF HEMATOSALPINX (blood-filled fallopian tube)
• Most important predisposing condition (present
in 35% to 50% of patients is prior PELVIC
INFLAMMATORY DISEASE resulting in Intraluminal
Fallopian tube scarring (Chronic Salpingitis)
 ECTOPIC PREGNANCY
• Risk of Ectopic pregnancy is also increased with
peritubal scarring and adhesions which may be
caused by Appendicitis, Endometriosis and
Previous surgery
• Use of Intrauterine Contraceptive Device is
associated with twofold increase of ectopic
pregnancy
• Growth of gestational sac distends the FT causing
thinning of the wall and rupture
• The rupture frequently results in massive
intraperitoneal hemorrhage (may be Fatal)
 PLACENTA
A. The placenta is a transient structure, consisting
of a maternal portion and a fetal portion.
B. Function
• The placenta permits the exchange of various materials between the
maternal and fetal circulatory systems. This exchange occurs without
mixing of the two separate blood supplies.
• It secretes progesterone, hCG, chorionic thyrotropin, and hCS, a lactogenic
and growth-promoting hormone.
• It also produces estrogen with the assistance of the liver and adrenal
cortex of the fetus.
• Decidual cells of the stroma produce prostaglandins and prolactin.
VAGINA
 VAGINA
• The vagina is a fibromuscular canal with a wall
that is composed of three layers:
an inner mucosa
middle muscularis
external adventitia.
• It is circumscribed by a skeletal muscle sphincter at its external
orifice.
• It lacks glands throughout its length and is lubricated by secretions
from the cervix and by seepage of the extracellular fluid from the
vascular supply of the lamina propria.
 VAGINA
The mucosa is composed of a thick, stratified
squamous nonkeratinized epithelium and a
fibroelastic connective tissue, the lamina propria.
1. The epithelium contains glycogen, which is used
by the vaginal bacterial flora to produce lactic acid,
an acid that lowers the pH during the follicular
phase of the menstrual cycle and inhibits invasion by
pathogens.
2. The lamina propria is a fibroelastic connective
tissue that is highly vascular.
C. MUSCULARIS: irregularly arranged layers
of smooth muscle (thin inner circular layer and
a thicker outer longitudinal layer) interspersed
with elastic fibers.
D. ADVENTITIA: composed of fibroelastic
connective tissue.
 It attaches the vagina to the surrounding
structures.
 LABIA MAJORA
fat-laden folds of skin
 hair and secretions
of sebaceous glands
and sweat glands are
present on their
external surfaces.
 LABIA MINORA
folds of skin that possess a core of
highly vascular connective tissue
containing elastic fibers.
They lack hair follicles, but their dermis
contains numerous sebaceous glands,
which open directly onto the epithelial
surface.
 VESTIBULE
• The vestibule is the
space between the two
labia minora.
• Glands of Bartholin
(mucus-secreting glands)
and numerous smaller
mucus-secreting glands
around the urethra and
clitoris (minor vestibular
glands) open into this
space.
 CLITORIS
• composed of two small, cylindrical erectile
bodies, which terminate in the prepuce-
covered glans clitoridis.
• It contains many sensory nerve fibers and
specialized nerve endings (e.g.,Meissner cor-
puscles and pacinian corpuscles).
MAMMARY GLANDS
• Mammary glands of both genders are
identical for the first decade
• Each mammary gland of the postpubertal
female is composed of numerous compound
tubuloalveolar glands, each with its own
lactiferous sinus and a duct that opens at the
apex of the nipple.
 RESTING MAMMARY GLANDS
in adult, nonpregnant women
composed of lactiferous sinuses and
ducts lined in most areas by a stratified
cuboidal epithelium, with a basal layer
consisting of scattered myoepithelial
cells.
A basal lamina separates the epithelial
components from the underlying stroma.
RESTING MAMMARY GLANDS
 ACTIVE (LACTATING MAMMARY
GLANDS)
• enlarged during pregnancy by the
development of alveoli.
• Alveolar cells (secretory cells)
line the alveoli of active mammary glands and are
surrounded by an incomplete layer of myoepithelial cells.

They are richly endowed with lipid droplets, and

vesicles containing milk protein (caseins) and lactose.
LACTATING MAMMARY GLANDS
 NIPPLE
• The nipple is composed of dense, irregular collagenous connective
tissue interlaced with smooth muscle fibers that act as a sphincter.
• It contains the openings of the lactiferous ducts.
• It is surrounded by pigmented skin (areola) that is more deeply
pigmented during and subsequent to pregnancy and contains the
areolar glands (of Montgomery).
CLINICAL CORRELATION:
BREAST CANCER
 BREAST CANCER
• Breast cancer may originate from the epithelium lining
the ducts (ductal carcinoma) or the terminal ductules
(lobular carcinoma).
• If breast cancer is not treated early, the tumor cells
metastasize via lymphatic vessels to the axillary nodes
near the affected breast and later via the bloodstream
to the lungs, bone, and brain.
• Early detection by self-examination, mammography, or
ultrasound has led to a reduction in the mortality rate
associated with breast cancer.
GENETICS OF BREAST CANCER:
• Deficiency or mutation in the gene BRCA1 has
been shown to decrease the stability or
elevate the incidence of the mutation rate of
tumor suppressor genes such as p53.
• It appears that mutations in the BRCA1 gene
result in incapacitation of the checkpoint at
G2-M of the cell cycle.
• These mutated cells have the capability to
proliferate unchecked.
Invasive Lobular Carcinoma Invasive Ductal Carcinoma
 SECRETIONS OF THE MAMMARY
GLANDS
Colostrum (protein-rich yellowish fluid) a.
Colostrum is produced during the first few days
after birth. b. It is rich in cells (lymphocytes,
monocytes), lactalbumin, fat-soluble vitamins,
and minerals and
c. contains immunoglobulin A (IgA).
MILK
• It is released from the
mammary glands via the
milk ejection reflex in
response to a variety of
external stimuli related to
suckling.
• The milk ejection reflex
involves release of
oxytocin (from axons in
the pars nervosa of the
pituitary gland), which
induces contraction of the
myoepithelial cells, forcing
milk into the larger ducts
and out of the breast.