Female Reproductive System

Dr. Christine Ayochok

January 22 & 24, 2013
Components:
1. Ovaries:
o Female gonads
o Contain ovarian follicles (produce estrogen) that promote development of ova
o Corpus Luteum
Follicle remnants after ovulation
Provide estrogen and progesterone
2. Uterine Tubes (Oviducts):
o Capture released ovum
o Primary site for fertilization
o Convey ovum to the uterus
3. Uterus: hollow muscular organ lined by mucous (endometrium) that undergoes cyclic changes
controlled by ovarian hormones
4. Vagina
o Tubular organ that directs spermatozoa to cervical canal
o Vaginal fluid: increases sperm motility
o Estrogen: causes epithelium to thicken and its cells to accumulate glycogen
5. External genitalia: numerous nerve endings: sexual arousal (Clitoris, Labia Majora and Minora)
Cyclic Changes
Roughly every 28 days between menarche and menopause
Changes in structures and activity of each organ, especially ovaries and uterus
Synchronization
o Crucial to normal reproductive function
o Pituitary FSH and LH that directly modulate follicle growth and development, and ovarian hormone
production
Ovarian hormones (estrogen, progesterone): control changes in uterine lining and influence FSH and LH
through negative feedback
OVARIES
General Organization
Yellow white in color
Paired, almond-shaped orangs (3 x 1.5. x 1 cm)
Germinal epithelium
o Outer covering
o Does not form oocytes (because it is located in the oocyte)
o Simple cuboidal epithelium derived from peritoneum
Tunica Albuginea
o Inner covering
o Dense CT capsule between germinal epithelium and cortex
Peripheral cortex: harbors most of oocyte-containing ovarian follicles embedded in a stroma
Central medulla: stroma containing rich vascular bed

Ovarian follicles
Each with a single oocyte surrounded by 1 or
more layers of follicle (granulosa cells)
Cortex
o Follicles at various stage of development
o Primordial, growing, mature, atretic
Primordial follicles
Inactive: earliest stage of follicle development
Predominant follicles present before puberty,
still constitute the majority thereafter
Each consists of a primary oocyte (most in
diplotene stage of meiosis I prophase)
surrounded by 1 layer of squamous follicle cells;
flattened
Oocyte
o Up to 26 u in diameter
o Pale, eccentrically placed nucleus with conspicuous nucleolus

Growing Follicles
o Growth stimulated by FSH
o Oocyte enlarges to 125 to 150 u
o Follicle epithelium becomes cuboidal and
proliferates to become stratified
(multilaminar)
o Stromal tissue surrounding follicle:
differentiates into steroid hormoneproducing theca folliculi
o Primary follicles
Primary oocyte surrounded by single or
multiple layers of cuboidal follicle cells
No antrum
Unilaminar
Single layer of cuboidal cells
Glycoprotein-rich zona pellicud
forms between oocyte and follicle cells
Multilaminar
Multiple layers of follicle cells
Zona pellucida thickens
Theca folliculi forms
Steroid secreting, coming from
the stroma

Secondary follicles
Cavities filled with fluid (liquor folliculi)
appear between the follicle cells,
gradually coalescing to form 1 large
cavity or antrum
Theca folliculi forms 2 layers
Theca interna: rich vascular
network and steroid secreting
cuboidal cells with abundant SER
Theca externa: mainly vascular
connective tissue

Mature (Graafian) Follicles

o Large diameter (2.5 cm)
o Immediately precedes
ovulation
o Antrum size increases greatly
o Oocyte displaced to one side
of the follicle, surrounded by a
few layers of follicle cells
(corona radiate)
o Oocyte rests on a pedestal of
follicle cells (cumulus
oophorus)
Atretic Follicles
o 400,000 follicles present at
birth
450 develop to maturity,
more than 99% become
atretic
o Atresia of primordial follicles
Leaves a space filled by stroma
o Primary and secondary follicles
Remnants removed by macrophages and replaced by stromal cells, with collagenous scar
Scar gradually removed and remodeled into normal stromal tissue

Origin and Maturation of Oocytes

Embryo
o Yolk sac endoderm gives rise to primordial cells that migrate to the genital ridges in posterior wall of
abdominal cavity
Germ cells
o Surrounded by flattened follicle cells
o Enter 1st meiotic division and arrest at prophase (primary oocytes)
o 1st meiotic division completed before ovulation (secondary oocytes)
o Ovum: secondary oocyte with almost all of the cytoplasm
o Other: 1st polar body
o Ovum begins meiosis II before ovulation, halts in metaphase until fertilization occurs
o Fertilization: meiosis II completed, with formation of 2nd polar body
o Zygote: fertilized ovum
Polar body will disintegrate thereafter
Ovulation
Day 14 of a 28-day cycle
Rupture o f a mature follicle and release of its ovum
Preceded and stimulated by a surge in LH
Ovum + zona pellucid + corona radiate detach from cumulus oophorus and float in antrum
Collagenase: stroma thins and becomes ischemic between follicle and ovary surface, indicating site of
imminent rupture (stigma)

Rupture: ovum + corona radiata intact

expelled by ovary and captured by
uterine tube
Ovum degenerates unless fertilized
within 24 hours

Corpus Luteum
Temporary endocrine gland
Formed by remnants of follicle after
ovulation
Cells in granulosa cell layer and theca
interna enlarge and secrete steroid
Granulosa lutein cells: large, palestaining, estrogen-secreting, derived
from theca interna
Corpus luteum of Menstruation
o Fertilization does not occur
o Degenerates after about 14 days
Corpus luteum of Pregnancy
o Enlarges and maintained for 6
months, gradually declines thereafter and persists until the end of pregnancy
o Secretes estrogen, progesterone
o Secretes relaxin
Polypeptide hormone that loses fibrocartilage
Attachment of Symphysis pubis, allowing pelvic
opening to enlarge during parturition
Depo provera, inhibits LH surge
Breast feeding, inhibits LH surge via increased Prolactin
Corpus albicans
Dense CT scar
Replaces a degenerated corpus luteum
Eventually removed by macrophages
Albicans (whitish in color) will eventually be replaced by
stromal tissue

Hormones and Ovarian Function

FSH: stimulates follicle growth during 1st half of menstrual cycle
Growing follicles produce estrogen, whose high mid-cycle levesl puts negative feedback on pituitary
gland thereby reducing FSH
Decreased FSH causes LH surge that directs follicle maturation, stimulates ovulation, control and
maintenance of corpus luteum
Corpus luteum: produces both estrogen and progesterone
Progesterone inhibits LH production, causing corpus luteum to degenerate after about 14 days (without
fertilization)
With fertilization
o Chorionic gonadotropin produced by developing placenta maintains corpus luteum in the absence
of LH
Sympathicotropic Cells (Burger Cells) Always aksed in practicals, located in the hilum
Hilum
Secrete testosterone
Epithelioid cells with clear cytoplasm
Central dark-staining nucleus
Seen as clusters

Vestigeal Organs associated with the Ovary

Parallel or diverging tubules in Mesovarium, extending from hilus of ovary toward oviduct and fuses
with longitudinal tubule parallel to oviduct, lined by cuboidal epithelium
4 vestigeal organs, name depends on its location:
1. Hydatid Cyst of Morgagni: cyst-like expansion of the upper end of the longitudinal tubule
2. Duct of Gartner: opposite end of longitudinal tubule extending some distance to uterus
3. Epophoron
o Transverse tubules and longitudinal duct of Gartner
Rudiment of nephrosis
Homolog of ductuli efferents and epididymis in males
4. Paraophoron
o Vestigial epithelium lined tubules in braid ligament between epoophoron and uterus
o Remnant of caudal portion of mesonephron, homologous to vestigial paradidymis in males
Clinical Correlation: normally seen intraoperatively
UTERINE TUBES
12 cm long muscular tubes
Lumen continuous with uterine cavity
Distal end opens to peritoneal cavity near ovary
Function
o Captures ovulated ovum
o Provides suitable environment (most common site of) for fertilization
o Transports zygote to uterus
Segments
Pars interstitialis (intramural)
o Penetrates uterine wall
o Fewest mucosal folds
o Most proximal
Isthmus
o Narrower segment adjacent to uterine wall
o Common site of ectopic pregnancy
Ampulla
o Widest segment
o Common site for fertilization
o Extensive branched mucosal folds
Infundibulum
o Funnel-shaped distal segment
o Fimbriae: finger-like extensions of mucosal folds
Wall structure

3 layers: Mucosa, Muscularis, Serosa

No Submucosa infection easily spreads
in the Muscularis
Mucosa
o Lining epithelium
o Lamina Propria
o Mucosal folds
Largest and most numerous in the
ampulla, infundibulum
o Lining
Simple columnar with 2 cell types
Ciliated columnar cells: most of
cells beat towards the uterus, thus
aiding in egg transport
Peg cells
Shorter, mucus-secreting
Secretions helps transport the
ovum and hinders bacterial
access to peritoneal cavity
Muscularis
o Inner circular, outer longitudinal smooth muscle layers
Contractions move the ovum toward the uterus
Serosa
o Outer covering of visceral peritoneum

Cyclic Changes
Most marked on fimbriae, infundibulum and upper ampulla
Diminish toward the isthmus
Follicular phase
o Epithelial cells enlarge and begin ciliogenesis
o Increased activity of peg cells
Peak at midcycle
Reversed in the luteal phase
Example
o Preovulatory phase
o Percentage of ciliated cells in the fimbriae 48%, decreased to 4% in the luteal phase
UTERUS
Pear-shaped muscular organ in pelvic cavity
Site of embryonic implantation and development
Gross: 3 regions
o Body (corpus): large, round, middle region
o Fundus: part of the body above the entry of the uterine tubes
o Neck (cervix): narrow, downward extension of uterus into vagina
Wall: 3 layers
o Endometrium
o Myometrium
o Serosa or Adventitia

Endometrium

Uterine mucosa
Simple columnar epithelium supported by lamina
Propria
Dual blood supply
o From Arcuate arteries (branch of uterine artery)
o Straight arteries to basale (retained during
shedding)
o Coiled arteries to functionale (lost during
shedding)
2 layers:
o Stratum functionale
Pars functionalis
Temporary layer at luminal surface
Responds to ovarian hormones by undergoing
cycling, thickening and shedding
Zona compacta (near lumen) and deeper zona spongiosa
o Stratum basale
Pars Basalis
Thinner, deeper, zona spongiosa
Contains basal portions of
endometrial glands
Retained during menstruation
Myometrium
Most conspicuous
Thickest tunic of uterus
4 poorly defined smooth muscle layers
Middle layers: contain Arcuate arteries
Pregnancy: myometrium grows via
hypertrophy (size) and hyperplasia
(number) to contain growing fetus
At birth Oxytocin stage: promotes forceful
myometrial contractions that expel fetus
Serosa
Covers fundus and most of the body
Menstrual Cycle
3 phases based on structural and functional
changes in endometrium
1. Menstrual
o 1st day of menses to days 3-5 of cycle
o Ischemia, degeneration, shedding of
functionalis
o Fragments of functionalis tissue along
with blood and uterine fluid are
discharged through vagina as menstrual
fluid
2. Proliferative (follicular phase
o Days 4 to 6 to day 14 of cycle
o Under influence of estrogen:
endometrium regenerates from basale
o Functionale thickens, glands lengthen
and remain straight
o *Follicular refers to ovary
o *Proliferative refers to endometrium
3. Secretory (Luteal) phase
o Days 15 to 28 of cycle
o Progesterone: edema of lamina Propria, endometrial thickening

o
o
o

Glands: highly coiled, saw-tooth appearance

Day 20: prepared to receive implanting embryo
Without implantation: cycle begins

Uterine Cervix
Inferior part of uterus
External surfaces bulges into vaginal
canal
Wall
o Mainly dense connective tissue
o Small amount of smooth muscle
Mucosa
o Tall columnar epithelium (ciliated
simple columnar)
o Branched cervical glands:
penetrate lamina Propria
o Stratified squamous epithelium:
external (vaginal) surface
o External os
Switch to epithelial type
Not shed during
menstruation
Ovulation: watery secretions permit
access by sperm
Luteal phase and pregnancy: Secretions abundant and more viscous
Preceding parturition: cervical dilatation in response to collagenase activity in cervical wall
Clinical correlation: Internal examination cervix is measured
Fertilization
Ampullaroisthmic junction
Sperm penetrate corona radiate and zona pellucida
1 sperm head fuses with oolemma
Induces completion of ovums meiosis II
Haploid male and female pronuclei: zygote
Zygote: several rounds of mitosis: morula
Cavity in embryo: blastocyst: enters uterus (day 4)
o Blastomeres: 2 layers: peripheral trophoblast and inner cell mass
Floats 2 to 3 days before implantation (zona pellucida dissipates to allow trophoblast cells to be in
direct contact with endometrium)
Implantation
Penetration of uterine epithelium by blastocyst
1st step in placentation
Blastocyst activity
o Trophoblast cells divide rapidly, differentiate into 2 layers
o Syncytiotrophoblast
o Highly invasive outer layer, multiple nuclei in a single large cytoplasm
o Formed by fusion of mononucleated cells from underlying layer (cytotrophoblast)
Day 9: embryo completely embedded in endometrium, surrounded by trophoblastic cells
Inner cell forms bilaminar disk (blastodisk) that becomes the embryo with a shell of extraembryonic
mesoderm
In between: extraembryonic coelom
Embryo separated from endometrium by colon
Chorion
o Includes derivatives of trophoblast and extra embryonic mesoderm: 2 regions

Chorion frondosum
Lies adjacent to decidua basalis
Forms fetal part of placenta
o Chorion laeve
Adjacent to decidua capsularis
Fuses with decidua parietalis midway through pregnancy
Decidual reaction
o Decidua: pregnant endometrium
o Endometrial changes: decidual reaction: helps prevent invasion of trophoblast beyond endometrium
(decidua increta /percreta)
o Stromal cells enlarge to become decidual cells (prolactin)
o 3 layers of decidua:
Decidua basalis: underlies implantation site, forms maternal part of placenta
Decidua capsularis: overlies implanted embryo, separating it from uterine cavity
Decidua parietalis / vera: remainder of endometrium
o

PLACENTA
Has embryonic (corpus frondosum) and extraembryonic (decidua basalis) components
Steps in placental development (placentation)
Syncytiotroph surrounds small islands of endometrium that contain blood vessels
Enzymes lyse maternal tissue, leaving lacunae and rupturing blood vessels
Blood vessels fill syncytiotroph-lined lacunae
Chorionic villi grow into these lacunae
Chorionic villi
o Bring blood in fetal blood vessels close enough to maternal blood in lacunae for exchange
o Selectively permeable placental border
o Definitive evidence for pregnancy than the decidua
Placentation
Primary villi: tongues of cyto and syncytiotroph
Secondary villi: syncytio, cytotroph, core of
extraembryonic mesenchyme (become blood
vessels that establish connections with umbilical
vessels of fetus and maternal circulation)
Tertiary villi: syncytio, cytotroph, entraembryonic
mesenchyme with blood vessels in its course

Placental Functions
Transfer of nutrients and wastes
o Day 23 AOG: fetal blood circulating through
tertiary villi
o Nutrients from maternal blood (lacunae) reach
fetal circulation by passing successively through the syncytiotroph, cytotroph, basal lamina of troph,
extraembryonic mesenchyme, basal lamina of blood vessels in tertiary villi, fetal vascular
endothelial cells
o Placental barrier: restricts substances crossing between 2 circulations
o Fimbrinoid: layer of products of necrosis that forms non-antigenic barrier
Placental hormones
o Syncytiotroph, decidual cells
o Chorionic gonadotropin, chorionic thyrotropin, chorionic corticotrophin, estrogens, progesterones,
prolactin, placental lactogen
o Cells that secrete hormone except cytotrophoblast
VAGINA
Extends from the cervix to the external genitalia
Walls lack glands

Vaginal lubrication: secretions from cervical and Bartholins glands and smaller mucus glands in
vestibule
o 3 layers: Mucosa, Muscularis, Adventitia
Mucosa
Stratified squamous epithelium rich in glycogen, elastic fiber-rich lamina Propria
Low pH: lactic acid accumulation due to bacterial metabolism of glycogen
Extensive capillary plexus in lamina Propria: fluid into lumen during sexual arousal!
Muscularis: mainly longitudinal smooth muscle, some circular fibers near mucosa
Adventitia
Dense connective tissue rich in elastic fibers
Extensive venous plexus, nerve fiber bundles, clusters of neurons
Clue cells: indicative of bacterial vaginosis
Glycogen is stained within cytoplasm, if without, indicative of malignancy or dysplasia
o

EXTERNAL GENITALIA
Richly innervated with Meissners and Pacinian corpuscles free nerve endings
1. Clitoris
o Homolog of dorsal part of penis
o Surrounded by prepuce, covered stratified squamous epithelium
2. Vestibule
o Receives vaginal and urethral openings
o Covered by stratified squamous epithelium
o 2 types of glands
Bartholins glands (glandulae vestibulares majores)
2 large tubulo-alveolar mucus glands on opposite sides of vestibule
Analogous to Cowpers glands in the male
Vestibular glands (glandulae vestibulares minores)
Smaller and more numerous mucus glands analogous to glands of Littre
3. Labia minora
o Skin folds with core of spongy (erectile) connective tissue
o Covered by stratified squamous epithelium
o Analogous to ale corpus Spongiosum
o Thin keratinized layer on surface
o Contain sweat and sebaceous glands
o Lack hair
4. Labia majora
o Folds of skin with a core of subcutaneous fat and thin layer of muscle
o Inner surface to that in labia minora
o Outer surface: numerous sebaceous and sweat glands
o Analogous to the scrotum in males