Female Reproductive System 1

Question 1

What does the female reproductive system consist of?

Answer 1

Consists of organs located in the pelvic
cavity as well as external genitalia.
• Ovary
• Uterine tube
• Uterus
• Placenta
• Vagina
• *Mammary glands
Many of these organs undergo hormone
mediated changes
• At puberty (menarche = 1st period)
• During the menstrual cycle • Pregnancy

Question 2

Summarize the structure function of the ovaries

Answer 2

Function:
• Produce gametes = oogenesis
• Secrete hormones = (steroidogenesis): estrogens and progesterone

Structure:

1. Germinal epithelium
2. Tunica albuginea
3. Cortex
4. Medulla (M):
5. Cyclic ovarian function is regulated by hormones from the pituitaryluteinizing and follicle stimulating hormones (LH &FSH)

Question 3

Summarize the histological structure of the ovaries

Answer 3

1. “Germinal” epithelium (GE)
   − Covers ovary; is continuous with mesovarium
   − Single layer of cuboidal cells (mesothelial origin)
   − 70% of ovarian cancer arise from the GE
2. Tunica albuginea
   − Deep to germinal epithelium
   − Dense connective tissue layer
3. Cortex
   − Peripherally located
   − Parenchyma: Follicles in different stages of development
   − Cellular rich Connective tissue
4. Medulla
   − Central portion
   − Loose connective tissue
   − Blood vessels/nerves/lymphatics

Question 4

explain oogenesis

Answer 4

1. Parenchyma: follicle with oocyte
2. Oogenesis and follicular development begins before
   birth
   I. Oogonia forms primary oocyte
   • ~600,000 – 800,000 by birth

II. Primary oocyte arrested in prophase of meiosis I
until puberty
• Lasts between 12-50 yearsrisk of
chromosomal anomalies

III. After menarche, mature every month
• Just before ovulation Meiosis I complete secondary oocyte (arrested in metaphase II)
• ~400 ovulated during reproductive years
IV. Meiosis complete at fertilization

Question 5

Summarize follicular development

Answer 5

The oocyte associates with ovarian follicular cells to form follicles
During follicle development, hormone-controlled changes occur in the oocyte, follicular cells and ovarian stroma.
1. Primordial follicle
2. Growing follicles:
I. Primary: A. Early B. Late II. Secondary
3. Mature/ Graafian
4. Atretic

Question 6

Summarize follicular phase of the ovary

Answer 6

Under influence of FSH & LH Development of follicles FSHGranulosa & Theca cells ESTROGEN - Principal Hormone
Late follicular phase
• Increased progesterone • LH surge
• Small FSH increase
• OVULATION

Question 7

What is the primordial follicle?

Answer 7

 Most numerous follicles
 Located just deep to the tunica albuginea
 Oocyte (size ~30μ)

• Primary oocyte in prophase I of meiosis Diploid (2n)
Further meiotic activity arrested
• Large eccentric nucleus, large nucleoli
 Follicular cells
• Single layer of squamous follicular cells surrounds oocyte
• Basal lamina separates follicular cells from stroma

Question 8

Describe the growing follicle:early primary

Answer 8

 Some (~10-20) follicles begin to mature at puberty  Primordial follicleearly primary follicle
 Deeper in cortical stroma
 Oocyte
• Primary oocyte enlarges (follicle ~50-80 μm)
• Secretes an Amorphous glycoprotein layer around itself
 Zona Pellucida
o Homogenous, refractile o Eosinophilic, PAS +
 Zona pellucida glycoproteins (ZP-1, ZP-2, ZP-3 & ZP-4)
• Sperm-binding receptor
• Induces acrosome reaction
 Follicular cells (FC)
• Follicular cells become cuboidal (unilaminar)

Question 9

Describe growing follicle: late primary

Answer 9

 Zona pellucida (ZP) is well defined:
• Processes of granulosa cells
• Microvilli of oocyte
 Follicular cells
• Multilayered mass (Multilaminar)
 Granulosa cells (GC) – Stratum granulosum
• Receptors for FSH
• Secrete aromataseandrostenedione to estrogen
• Distinct basal lamina
 Adjacent stroma forms Theca folliculi
1. Theca interna (TI)
― Highly vascularized area close to basement membrane
― Receptors for LH (and LDL)
― Steroid-secreting cells
― Produce androstenedione (precursor of estrogen)
2. Theca externa (less defined)
― connective tissue and smooth muscle

Question 10

Describe the growing follicle: secondary (Antral)

Answer 10

 Oocyte
• Eccentric position; Size 125μm
• No further growth
 Stratum Granulosum
• •
•
6-12 layers of granulosa cells surround oocyte Appearance of Antral spaces containing liquor folliculi
 Secreted by granulosa cells
o Hyaluronan and hormones o Oocyte maturation inhibitor
Granulosa cells begin to organize into a thickened mound
 Theca layers are more defined
• Basal lamina between theca interna and granulosa

Question 11

Describe the mature or Graafian follicle

Answer 11

Located close to ovarian surface (bulge) Extends through full cortical thickness Large (≥ 10mm) at ovulation
 Oocyte
• Primary oocytesecondary oocyte just before ovulation
 Stratum Granulosum (SG)
• Single large crescent-shaped antrum
• Cumulus oophorus (CO):
 ”hillock” of cells connecting oocyte to follicular wall
• Corona radiata:
 1-2 layers cells lining oocyte
 Microvilli of these cells and oocyte communicate via
gap junctions
• Membrana granulosa  remaining mural granulosa cells
surrounding antral lumen
 Thin stratum granulosum
 Theca layers thick and well defined

Question 12

Describe the collaborative synthesis of hormones

Answer 12

 Theca Interna
• LH receptors – stimulate androgen production
• Secrete Androgens
 Granulosa cells
• FSH receptors – stimulate aromatase activity
• Secrete aromatase: convert androgens to estrogen
• Which area of cells have highest aromatase activity?
 Estrogens stimulate granulosa proliferation • further increase in estrogen (estradiol)
• *Net rapid increase in follicle size

Question 13

What are the functions of hormones and ovarian surface in pre-ovulation?

Answer 13

 Hormones
• Estrogensensitization of LH and FSH to GnRH
• LH surge (~24 hours before ovulation)
Smaller FSH increase
• Follicle
Desensitization of LH receptors
Decreased estrogen production
• Oocyte
Primary oocyte completes first meiotic division
forms secondary oocyte & first polar body Which follicle?
Immediately enters second meiotic division - arrested at metaphase II

 Ovarian Surface
• Cessation of blood flow to surface over bulge
• Follicular Stigma
Elevates, then ruptures (Indication of impending ovulation)

Question 14

What causes ovulation?

Answer 14

 Increase follicular fluid volume and pressure • Spaces between granulosa cells enlarge
 Follicular wall proteolysis + GAG deposition
• Oocyte + cumulus cells loosen from GC
• Corona radiata becomes single layer
 Smooth muscle contraction in theca externa
 Secondary oocyte (+ corona radiata) released
 Meiosis II complete ONLY upon fertilization
 Failure of fertilization leads to degeneration of the oocyte.

Question 15

Describe the luteal phase of ovary

Answer 15

Begins after ovulation

Formation of Corpus Luteum

PROGESTERONE - Principal Hormone

LH responsible for maintenance of corpus luteum

Degeneration of corpus luteum without fertilization

Question 16

What are the significance of Corpus Hemorrhagicum and Luteum?

Answer 16

 After ovulation: follicle wall collapses, thrown into folds
 Corpus hemorrhagicum
• Filled with blood (thecal capillaries)
 Corpus Luteum (CL)
Stromal CT invades cavity (FC)
Luteinization of Granulosa and Theca Interna cells
 Increase size, fill with lipid droplets
Secretes hormones:
Inhibit LH + FSH (prevent follicle development & ovulation)
Prepares the uterus for implantation CL of menstruation (no fertilization):
− Declines after 10 days
CL of pregnancy (fertilization):
− first few (~8) weeks of pregnancy (declines as placenta develops)

Question 17

What are the functions of the corpus Luteum ?

Answer 17

Cells have features characteristic of steroid production:
− Lipids and lipochrome pigment- yellow appearance
− SER, abundant mitochondria with tubular cristae
1. Membrana granulosaGranulosa Lutein cells (GLC)
− Large, round cells with spherical nuclei
− 80% of cells
− Central location
− Secrete: progesterone, inhibin and estrogen
2. Theca internaTheca Lutein cells (TLC)
− Smaller, more deeply staining cells with spherical
nuclei
− 20% of cells
− Peripheral location scattered between GLC
− Secrete: progesterone and androgens

Question 18

What is the Atretic follicle?

Answer 18

 Several follicles develop during oogenesis, menstrual cycles
 Usually, ONE ovum released (ovulation)
 Others degenerate  Atretic follicles
 Mediated by apoptosis
• Smallerfollicles
Oocyte and GC shrink, degenerates Disappears from stroma
• Larger follicles:
Oocyte + GC: apoptotic changes
Zona pellucida: prominent, distorted (fold or collapse)
Glassy Membrane: thickening of BM between GC and TI
Theca cells: Interstitial glands
o Cluster of epithelioid cells – continue secreting hormones

Question 19

What are Polcystic ovaries?

Answer 19

• Excessive androgenestrogen
• Graafian follicle fails to mature
anovulatory cycle
• Anovulatory cycles result in infertility
Findings
  -enlarged ovary
  -Thick tunica albuginea (TA)
     -Impairs ovulation 
  -Multiple fluid fill cavities—> follicular cysts

Question 20

What are the structures/functions of ovarian/Fallopian tubes/ ovarian ducts?

Answer 20

 Pair of fibromuscular tubes, 10-12 cm
 Functions
• Conduct ova expelled from ovary to the uterus.
• Provide environment for fertilization*
 Parts
• Infundibulum
• Ampulla*
• Isthmus
• Intrauterine (intramural)
 Layers
• Serosa
• Muscularis 
• Mucosa
Mucosa forms longitudinal folds—>well defined infundibulum and ampulla.

Question 21

Describe the histology of uterine tubes

Answer 21

Mucosa – simple columnar epithelium with 2 cell types:
 Ciliated columnar epithelial cells (above)
• Most numerous in infundibulum + ampulla (almost 75%)
• Number of cells increased by estrogen (Which phase?)
 Secretory cells or peg cells (arrows and below )
• Non-ciliated
• Wedged between ciliated cells (arrow)
• Number of cells increased by progesterone (Which phase?)
• Secretes nutritive material for ovum.
 The ciliated cells keep the fluids secreted by the peg cells in motion
 Oocyte is carried along the tube by Ciliary movements and peristaltic muscular activity

Question 22

What are the layers of the uterine tubes?

Answer 22

Mucosa:
 Mucosal folds more prominent in the infundibulum

 Peg cells increase and ciliated cells decrease towards uterus
Muscular layer

 Thicker in intramural region

Question 23

What is the uterus?

Answer 23

 Muscular pelvic organ

 Provides protective and nutritive
environment for the fetus

 Three Anatomical Parts: • Fundus
• Body
• Cervix.

 Three Histological Layers:
• Endometrium: Mucosa (glandular)
• Myometrium: Muscular
• Perimetrium: Outer serosa/ adventitia

 Endometrium and myometrium undergo cyclic changes:
• Menstrual cycle

Question 24

Give the general structure of the endometrium

Answer 24

General Structure
 Simple columnar epithelium
 Simple tubular glands
 Lamina propria (endometrial stroma):
Mesenchymal like connective tissue
 Highly vascularized

Question 25

What are the layers of the endometrium?

Answer 25

1. Stratum functionale
   − Surface epithelium
   − Superficial portion (remainder) of glands
   − Supplied by branches of spiral arteries
   − Changes dramatically during the menstrual cycle
   − Sheds as menstrual debris if pregnancy does not occur

2. Stratum basale (~1mm)
− Stem cell niche of the functionale − Basal portion (origin) of glands
− Lower portion spiral arteries
− Retained during menstruation
− Close to myometrium

Question 26

What are the ovarian hormones and uterus?

Answer 26

 Pituitary gonadotrophins regulate ovarian follicle maturation after puberty

 Ovarian follicle development (ovarian
cycle) results in sex hormone release
• Follicular phase
• Luteal phase
 Affects the uterus—>Preparation for implantation
 Changes in the uterine lining—> menstrual cycle

Question 27

Summarize the menstrual cycle

Answer 27

 Cyclical changes that occur in the endometrium in response to ovarian hormones

 Typical cycles
 28 days long
 Ovulation at day 14

 Phases:
− Menstrual (Day 0 of cycle)
− Proliferative
− Secretory

Question 28

Describe the proliferative phase of the menstrual cycle

Answer 28

 After menses  5th to 14th day of the cycle

 Under influence of ovarian estrogen

 Also called estrogenic phase Which ovarian phase?
 Stratum Functionale proliferates:
• Epithelial cells – reconstitute glands

 Narrow lumens, relatively straight/ slightly wavy  Basal glandular cells accumulate glycogen
• Endothelial cells – lengthening of spiral arteries  Slightly coiled, lower 2/3 of functionale
• Stromal cells – proliferate, make CT
 Endometrium reaches thickness of ~3mm

Question 29

Describe the secretory phase of the menstrual cycle

Answer 29

 1-2 days after ovulation.
 Under the influence of progesterone
 AKA progesterone phase Which ovarian phase?
 Stratum functionale hypertrophies:
• Glands elongate, coil and dilate
Mucoid secretions: glycogen and glycoproteins
• Spiral arteries highly coiled and longer Extend to superficial part of stratum functionale
• Endometrium becomes edematous Stromal cells filled with glycogen
• Endometrium attains its greatest height (~5-6mm)
 Divided into:
• Early secretory phase
• Late secretory phase

Question 30

Differentiate the early and late secretory phase of the menstrual phase

Answer 30

Early

― More epithelium than glands
― Glands slightly elongated & coiled
― Spiral arteries 2/3 into functionale

Late

― Glands: elongated, coiled (saw-tooth), dilated (sacculated)
― Cells and glands filled with glycogen, glycoprotein
― Spiral artery in superficial part of stratum functionale

Question 31

Describe the menstrual phase of the menstrual cycle

Answer 31

 Due to decline in progesterone How long after ovulation?
• Periodic contraction of spiral arteries
• Ischemia around day 28
• Glands degenerate, endometrium shrinks
• Rupture of blood vessels
 Functional layer sheds menstruation • Blood, fluid, necrotic stroma + epithelium
 Only Basale remains intact: straight (proximal spiral) arteries intact
 Lasts ~5 days