Objectives
• Describe the anatomy of the female reproductive
system
• Describe the histology of the ovary including
polycystic ovary syndrome, ovarian cancer
• Describe the hormonal control of the ovary and
how it interacts with the uterus
• Describe the uterine tubes including ectopic
pregnancy
• Describe the uterus including fibroids,
endometrial cancer and endometriosis
• Describe the histology of the cervix including
cervical cancer
• Describe the histology of the vagina
Key Word List Female Repro
Ovary, Uterine/Fallopian tube, uterus, broad ligament, peritoneum, fertilization, ovarian &
Uterine artery, fimbriae, infundibulum, ampulla, isthmus, intramural part, peg cells, ciliated
Cells, endometrium, Myometrium, perimetrium, GNRH, portal system, FSH, LH, estrogen,
progesterone, germinal epithelium, cortex, medulla, follicles, primary oocyte, primordial
follicle, primary follicle, zona pellucida, antral/secondary follicle, Graafian/mature follicle,
granulosa cells, theca cells, corpus luteum, ovulation, corpus albicans, atretic follicle, antrum,
Liquor folliculi, corona radiata, androstenedione, polycystic ovaries, amennorhea, ovarian
cancer, BRCA 1, 2, ovarian cycle, uterine/endometrial/menstrual cycle, meiosis, fertilization,
zona reaction, zygote, ectopic pregnancy, endometriosis, tubular glands, stratum functionalis,
stratum basalis, menarche, menopause, menstruation, proliferative phase, secretory phase,
menstrual phase, ‘saw-tooth’ appearance, endometrial cancer, biopsy, adenocarcinoma,
oxytocin, uterine fibroids, leiomyosarcoma, cervix, endocervix, ectocervix, transformation
Zone, SCJ (squamocolumnar junction) Pap smear, cervical glands, Nabothian cysts, cervical
Cancer, HPV, cervical neoplasia, vagina, glycogen, lactic acid,
Describe the anatomy of the
female reproductive system
Ovaries
Oviducts
(Fallopian tubes)
Uterus
Cervix
Vagina
External Genitalia
“MENARCHE,
MENOPAUSE”
Ovaries
“Fimbriae”
Uterine Tube
Uterus
Bladder
The ovary, uterine tube and much of the uterus are
overlain by peritoneum and therefore have a serosa
Anastomotic blood supply from the ovarian,
uterine and vaginal arteries
Gartner’s Histology
Gartner’s Histology
Describe the histology of the ovary
including polycystic ovary syndrome
and ovarian cancer
Endocrine
Activity of
Ovary
Follicle
Types
FSH, LH Antral follicle Graafian follicle
Multilaminar
Primary follicle
Primary
follicle
Medulla
Primordial
follicle
Germinal
epithelium
Corpus albicans Corpus luteum
Primordial follicles
• Most abundant before
birth
• Primary oocyte
arrested in the
prophase stage of
meiosis I
• Surrounded by a single
layer of squamous
follicular cells (have
receptors for FSH)
Primordial ovarian follicles. surface epithelium (SE), tunica albuginea (TA), oocyte (O)
surrounded by a layer of flat epithelial follicular cells (arrows), are present in the ovarian
connective tissue (stroma).
Primary follicle
•Follicular cells change from squamous to cuboidal.
•Simple cuboidal epithelium = unilaminar primary
follicle.
•When the follicular cells proliferate and stratify,
forming several layers of cells around the primary
oocyte, the follicle is called a multilaminar primary
follicle, and the follicular cells are referred to as
granulosa cells.
•During this stage, a glycoprotein coat called the
zona pellucida surrounds the oocyte.
•Microvilli of the oocyte and filopodia of the
follicular cells invade the zona pellucida and form
gap junctions through which they communicate
throughout follicular development.
Cuboidal follicular cells
Primary follicles. primordial follicles (PF) and their flattened follicles cells (arrows), unilaminar
primary follicles (UF) granulosa cells (G) primary oocyte (O). ZP (zona pellucida)
Secondary Follicle
Antrum is present.
Many become
“atretic”
Corona
Radiata cells
Mature (Graafian) follicle
• Antrum is large
• Oocyte and corona radiata extend into the
antrum supported by granulosa cells (cumulus
oophorus)
• Stromal cells next to the granulosa cells
surrounding the antrum begin to differentiate
into the “theca interna”
• The theca interna is highly vascular and produces
androstenedione (a male hormone) which
granulosa cells convert to estrogen
Theca interna and externa
• The theca interna is
separated from the
granulosa cells by a
thickened basement
membrane
• The theca externa is the
surrounding connective tissue
A = antrum containing
‘liquor folliculi’
Antrum surrounds the oocyte
ESTROGEN
Granulosa cell
Following ovulation, the remaining
granulosa cells and theca interna
form the CORPUS LUTEUM which
secretes progesterone.
Corpus
Luteum
(a postovulatory
structure)
Ovary
• If pregnancy does not occur (hCG is not
produced) the corpus luteum degenerates
and forms the corpus albicans.
Polycystic ovary syndrome (PCOS)
• Genetic
• High circulating androgen levels
• Failure to ovulate- “cysts”
Effect on Ovary
Ovarian Hormones
Effect on Endometrium
Estrogen and progesterone produced by ovarian follicles regulate
the menstrual cycle (aka “uterine ”, “endometrial”)
2) Primary Oocyte
arrested at Prophase Meiosis I
(fetal ovary to puberty) 3) Completion of
Meiosis I during
ovulation
First polar body
4) Secondary
Oocyte
arrested at
Metaphase of
Meiosis II
5) Completion
of Meiosis II
1) Development of following
Primordial Follicle in the Second polar body sperm entry
fetal ovary
Gray’s Anatomy Fertilization of (2° oocyte)
LP
Lumen
CC NCC
Short, non-ciliated cells: Peg cells
(nourishment, immunity, sperm
capacitation) 100x
• Layers :
– Endometrium Isthmus
– Myometrium
– Perimetrium
serosa (or
adventitia)
Uterine glands
Stratum
vasculare
• The endometrium, or mucosal lining of the
uterus, is composed of a simple columnar
epithelium and a lamina propria.
• The epithelium is composed of nonciliated
secretory columnar cells and ciliated cells.
• The lamina propria houses simple branched
tubular glands that extend as far as the
myometrium .
• The morphological and physiological
alterations that occur in the endometrium
during the phases of the menstrual (uterine)
cycle are controlled by hormones.
Endometrium
• Epithelium and lamina propria
with tubular glands (simple but
with branches in the deeper
portions)
– Stratum Functionalis –
replaced every menstrual
cycle
– Stratum Basalis –
renewal of the
endometrium, remains
relatively unchanged
Blood Vessels of the Endometrium
• Uterine artery -
Arcuate arteries are
circumferentially oriented
arteries in the middle layers
of myometrium
• Radial artery -
From them straight
and coiled arteries branch
• Proliferative phase –
& follicular phase, from
day 6 to day 14
• Secretory phase –
& luteal phase, from day
15 to day 28
• Menstruation, which begins on the day
bleeding from the uterus starts, occurs when
fertilization does not take place.
• The corpus luteum becomes nonfunctional
about 14 days POSTovulation, thus reducing
the levels of progesterone and estrogen.
• Although the entire functionalis layer of the
endometrium is sloughed, it is not completely
released from the wall immediately; rather,
this process continues for 3 to 4 days.
Proliferative phase of Endometrium
• Occurs at the same time as
the follicular phase
• Begins when the menstrual
flow ceases (~day 4) and
continues through day 14
when the functionalis layer
is regenerated.
• Full complement of
epithelium, glands, stroma,
and SPIRAL arteries now
exists.
Proliferative phase of Endometrium
• Day 5-14 (right after menses)
• Coincides with follicular phase of ovarian cycle.
• Stratum functionalis regenerates - high mitotic activity
in the cells of the basal glands.
• Glands are straight & lined by simple columnar
epithelium.
• Spiral arteries elongate but remain convoluted; extend
from the basal layer into the functional layer
Late
proliferative
Phase
Glandular changes
Secretory phase of Endometrium
• Commences after ovulation
• Endometrium continues to thicken
Endometrial tissue
present in abnormal
locations
responds to hormonal
changes
Robbins’ Pathology
Endometriosis and adhesions
Endometrial cancer
• Endometrial cancers are the most common gynecologic cancers
in the United States, with over 35,000 women diagnosed each year.
The incidence is on a slow rise secondary to the obesity epidemic.
• The most common subtype, endometrioid
adenocarcinoma, typically occurs within a few decades of
menopause, is associated with obesity,
excessive estrogen exposure, often develops in the setting
of endometrial hyperplasia, and presents most often with vaginal
bleeding. Endometrial carcinoma is the third most common cause
of gynecologic cancer death (behind ovarian and cervical
cancer).
• Type 1 (~90%) occurs at menopause and is less aggressive than type
2 (~10%) which occurs a number of years after menopause.
• A total abdominal hysterectomy (surgical removal of the uterus)
with bilateral salpingo-oophorectomy is the most common
therapeutic approach.
Endometrial Cancer
Endometrial cancer can present in a
number of forms
Myometrium
• Middle layer – smooth muscle
– stratum vasculare
“Leiomyoma”
Describe the histology of the
cervix including cervical cancer
Uterine cervix
• Endocervix: mucus-secreting
simple columnar epithelium
• Ectocervix: lined by stratified
squamous epithelium
• Cervical glands – extensively Endo
branched mucous glands
• 85% is made of dense
connective tissue
Ecto
Cervical - Cervical canal –
Histology endocervix lined
by simple
columnar
epithelium
Ectocervix – lined by
stratified squamous
epithelium
Cervical glands
MRI
Blockage of the openings of the cervical
mucosal glands frequently results in the
accumulation of secretory products within
the glands, leading to the formation of
dilated Nabothian cysts – benign cysts
Cervix
• Branched cervical glands
secrete a serous fluid
close to ovulation.
Normal Abnormal
• In a study of 108,000 women ages 12-26,
those who got all three HPV vaccinations
had an overall 54% decreased level of
cervical dysplasia.
• E. Crowe et al. Effectiveness of quadrivalent
human papillomavirus vaccine for the
prevention of cervical abnormalities: case-
control study nested within a population
based screening programme in
Australia. BMJ. Vol. 348, March 4, 2014. doi:
10.1136/bmj.g1458.
Describe the histology of the vagina
VAGINA: Lumen
Mucosa, muscularis, adventitia
Aglandular
Stratified squamous
epithelium-
contains GLYCOGEN used to
create an acidic environment
(pH 3.8 – 4.5)
Development of the
3. Mammary cords
Mammary Gland become hollow and some
luminal epithelial cells
differentiate into
myoepithelium cells
List the basic tissue types found
in the mammary gland
• Epithelium
– Integument (skin)
– Ducts and secretory portion of glands
• Connective tissue
– Dense connective tissue (Cooper’s ligaments)
– Loose connective tissue
– Adipose tissue
• Muscle
– Myoepithelial cells
– Smooth muscle
• Nerve
– Sympathetic innervation
– Sensory innervation
Describe the structure of the
mammary gland
Mammary Gland:
Glandular appearance
at different stages
of function
Pathway:
Alveolus
Duct
Lactiferous Duct
Lactiferous Sinus
Nipple
Glandular epithelium (ducts
and lobules) surrounded and
supported by dense irregular
and adipose connective tissue
The nipple: The duct system of an
•many lactiferous sinuses inactive gland blindly
•smooth muscle ends in small alveoli
•sympathetic nerve fibers
Sebaceous glands:
Not associated with hair follicles
Changes in the mammary gland
During pregnancy
In non-pregnant During lactation alveoli are
alveoli proliferate
women the gland fully differentiated with
at the ends of
has an inactive abundant milk secretion.
ducts and prepare
duct system.
for milk secretion.
Nonpregnant Pregnant Postpartum
Mammary Gland
The Mammary Gland during Pregnancy:
Proliferation of ducts and development of secretory alveoli
Alveoli surrounded by
Interlobular dense irregular intralobular loose connective tissue
connective tissue
http://faculty.tcc.edu/mmitchell/histo/mam2.htm
The lactating Mammary Gland:
Prolactin stimulates secretion of milk by alveolar cells
Lactiferous duct
Distended alveoli
Inactive
Active
Describe the hormonal regulation of
the mammary gland
• Estrogen- mesenchymal cell
proliferation especially adipose
cells
• Progesterone- maturation of
secretory capability
• Prolactin- initiation of secretion
• Oxytocin- milk ejection (tgt:
myoepithelium)
The Mammary Gland at Puberty and Pregnancy
Progesterone
stimulates the
formation of
alveolar buds
Transition from development to
lactation
• Estrogen and progesterone inhibit the
lactogenic (milk producing) effect of prolactin
• The placenta is the primary source of these
hormones during the fetal period
• At birth, the placenta is extruded and the
levels of estrogen and progesterone drop
dramatically
• The lactogenic effect of prolactin is no longer
inhibited and milk production ensues
Note
• If the entire placenta is not extruded
during birth, the remnants may produce
enough progesterone to inhibit milk
production.
Anterior Pituitary
Acidophilic mammotrophs
Sensory (neural) regulation of
hormones
Sensation from the nipple due to suckling:
• Inhibits the release of PIF (prolactin-
inhibiting factor): Result: more prolactin
available
• Stimulates the release of oxytocin which
causes contraction of myoepithelial cells
which results in milk ejection
Neurohormonal Reflex of
OXYTOCIN:
At parturition, OXYTOCIN
stimulates UTERINE SMOOTH
MUSCLE contraction to
expel fetus and fetal membranes.
Netter’s
Describe the secretions of the
mammary gland
LIPIDS: LACTOSE:
released surrounded by a rim of produced in the Golgi and
cytoplasm (apocrine secretion) released into the alveolar lumen
PROTEINS:
IgA: (casein, lactalbumin)
produced by plasma secreted by a
cells is shuttled merocrine mechanism
across the epithelium
PROLACTIN:
First Milk= stimulates milk production
Colostrum OXYTOCIN:
stimulates milk release
by inducing contraction of
myoepithelial cells
Discuss lactational amenorrhea
and cessation of lactation
Lactational amenorrhea
• ~50% of women do not experience menstrual
cycles during lactation
• High prolactin levels inhibit LH
• As a result they will not become pregnant
while nursing
• Used as a form of birth control in some
cultures
• Most effective during first 6 months after
pregnancy
Cessation of lactation
• Neural stimulation from suckling promotes
prolactin release
• Cessation of suckling discontinues prolactin
release
• Glandular tissue becomes inactive
Discuss Breast cancer
Breast Cancer
• Hormonal exposure (increases with age, early
menarche, late menopause)
• Genetic predisposition- BRCA1, BRCA2 (1 in 20
cases) HER2 (more aggressive cancers)
• Usually forms from ductal epithelium (ductal
carcinoma) or lobules (lobular carcinoma)
• Most common cancer in women (~30% of cancers
in females)
• 200,000 cases in the US per year (1,700 in males)
• 5 year survival rate about 4 out of 5
Staging
• Stage 0 is a pre-cancerous or marker
condition, either ductal carcinoma in
situ (DCIS) or lobular carcinoma in situ (LCIS).
• Stages 1–3 are within the breast or regional
lymph nodes.
• Stage 4 is 'metastatic' cancer that has a less
favorable prognosis.
One use of lymph
node knowledge
Ductal carcinoma in situ
Ductal carcinoma
Ductal cancer metastasis
Invasive/in situ ductal carcinoma
http://www.sciencedaily.com/releases
/2011/04/110419164213.htm
• "There is an inherent connection between
inflammation and cancer," explained Li. "In
the case of breast cancers, a medical review
systematically tabulated IL-6 levels in various
categories of cancer patients, all showing that
IL-6 levels elevated up to 40-fold, especially in
later stages, metastatic cases and recurrent
cases."
Fallopian Tubes Uterus:
• 10 cm long and 1 cm in diameter • Muscular pear shaped organ on top of bladder
• Receive mature ovum from ovary • Linings: Perimetrium, Myometrium and Endometrium.
• Provide site for fertilization – Peri: peritoneal,
• Enter uterus through isthmus – Myo: Muscular,
– Endo: innermost
• Other end, is ampulla ends in infundibulum • Sphincter of uterus=Cervix
with fimbriae
• Not directly connected to ovaries
Vagina:
Ovaries: • Receptive organ for penis
• Produce Gamete • Opening between urethra, and anus.
• Rich in Glycogen and bacterial
• 3 cm long solid mass of cells conversion to lactic acid keeps vagina
acidic.
• Suspended in the abdomen
by ligaments and
mesenteries External genitalia
• Clitoris: Penis-like organ, chiefly erectile tissue.
• Labia: folds of skin
• L. Majora: Thick and is covered with pubic hair, protective
function
• L. Minora: thin membranes
Ovary- Summary
• Germinal epithelium (CA),
tunica albuginea, stroma,
medulla
• Ova, granulosa cells,
theca interna
• Follicular maturation,
ovulation, corpus luteum,
corpus albicans
• Production of estrogen
and progesterone
regulated by FSH and LH
Fallopian tube - Summary
• Fallopian tube:
– Fimbrial end – to receive released
ovum
– Ampulla site of fertilization
• Mucosa consists of
– Thrown into numerous folds
especially in the ampulla.
– ciliated &
– secretory non-ciliated cells –
nutrient rich fluid
• Inner circular & outer longitudinal
muscle layer.
• Serosa – outermost covering
containing mesothelium.
Uterus - Summary
• Endometrium – cyclical changes
• Proliferative – regrowth of stratum
functionalis
– simple tubular glands
– Mitosis seen
– Estrogen
Adventitia is fibroelastic
connective tissue.
Key Word List Female Repro
Ovary, Uterine/Fallopian tube, uterus, broad ligament, peritoneum, fertilization, ovarian &
Uterine artery, fimbriae, infundibulum, ampulla, isthmus, intramural part, peg cells, ciliated
Cells, endometrium, Myometrium, perimetrium, GNRH, portal system, FSH, LH, estrogen,
progesterone, germinal epithelium, cortex, medulla, follicles, primary oocyte, primordial
follicle, primary follicle, zona pellucida, antral/secondary follicle, Graafian/mature follicle,
granulosa cells, theca cells, corpus luteum, ovulation, corpus albicans, atretic follicle, antrum,
Liquor folliculi, corona radiata, androstenedione, polycystic ovaries, amennorhea, ovarian
cancer, BRCA 1, 2, ovarian cycle, uterine/endometrial/menstrual cycle, meiosis, fertilization,
zona reaction, zygote, ectopic pregnancy, endometriosis, tubular glands, stratum functionalis,
stratum basalis, menarche, menopause, menstruation, proliferative phase, secretory phase,
menstrual phase, ‘saw-tooth’ appearance, endometrial cancer, biopsy, adenocarcinoma,
oxytocin, uterine fibroids, leiomyosarcoma, cervix, endocervix, ectocervix, transformation
Zone, SCJ (squamocolumnar junction) Pap smear, cervical glands, Nabothian cysts, cervical
Cancer, HPV, cervical neoplasia, vagina, glycogen, lactic acid,
Fallopian Tubes Uterus:
• 10 cm long and 1 cm in diameter • Muscular pear shaped organ on top of bladder
• Receive mature ovum from ovary • Linings: Perimetrium, Myometrium and Endometrium.
• Provide site for fertilization – Peri: peritoneal,
• Enter uterus through isthmus – Myo: Muscular,
– Endo: innermost
• Other end, is ampulla ends in infundibulum • Sphincter of uterus=Cervix
with fimbriae
• Not directly connected to ovaries
Vagina:
Ovaries: • Receptive organ for penis
• Produce Gamete • Opening between urethra, and anus.
• Rich in Glycogen and bacterial
• 3 cm long solid mass of cells conversion to lactic acid keeps vagina
acidic.
• Suspended in the abdomen
by ligaments and
mesenteries External genitalia
• Clitoris: Penis-like organ, chiefly erectile tissue.
• Labia: folds of skin
• L. Majora: Thick and is covered with pubic hair, protective
function
• L. Minora: thin membranes
Ovary- Summary
• Germinal epithelium (CA),
tunica albuginea, stroma,
medulla
• Ova, granulosa cells,
theca interna
• Follicular maturation,
ovulation, corpus luteum,
corpus albicans
• Production of estrogen
and progesterone
regulated by FSH and LH
Fallopian tube - Summary
• Fallopian tube:
– Fimbrial end – to receive released
ovum
– Ampulla site of fertilization
• Mucosa consists of
– Thrown into numerous folds
especially in the ampulla.
– ciliated &
– secretory non-ciliated cells –
nutrient rich fluid
• Inner circular & outer longitudinal
muscle layer.
• Serosa – outermost covering
containing mesothelium.
Uterus - Summary
• Endometrium – cyclical changes
• Proliferative – regrowth of stratum
functionalis
– simple tubular glands
– Mitosis seen
– Estrogen
Adventitia is fibroelastic
connective tissue.
Key Word List Female Repro
Ovary, Uterine/Fallopian tube, uterus, broad ligament, peritoneum, fertilization, ovarian &
Uterine artery, fimbriae, infundibulum, ampulla, isthmus, intramural part, peg cells, ciliated
Cells, endometrium, Myometrium, perimetrium, GNRH, portal system, FSH, LH, estrogen,
progesterone, germinal epithelium, cortex, medulla, follicles, primary oocyte, primordial
follicle, primary follicle, zona pellucida, antral/secondary follicle, Graafian/mature follicle,
granulosa cells, theca cells, corpus luteum, ovulation, corpus albicans, atretic follicle, antrum,
Liquor folliculi, corona radiata, androstenedione, polycystic ovaries, amennorhea, ovarian
cancer, BRCA 1, 2, ovarian cycle, uterine/endometrial/menstrual cycle, meiosis, fertilization,
zona reaction, zygote, ectopic pregnancy, endometriosis, tubular glands, stratum functionalis,
stratum basalis, menarche, menopause, menstruation, proliferative phase, secretory phase,
menstrual phase, ‘saw-tooth’ appearance, endometrial cancer, biopsy, adenocarcinoma,
oxytocin, uterine fibroids, leiomyosarcoma, cervix, endocervix, ectocervix, transformation
Zone, SCJ (squamocolumnar junction) Pap smear, cervical glands, Nabothian cysts, cervical
Cancer, HPV, cervical neoplasia, vagina, glycogen, lactic acid,