Female Reproductive

Question 1

Reproductive Period

Answer 1

1. Menarche: beginning of reproductive phase
2. Menstrual cycle: every ~ 28 days
   
   • Controlled by GnRH from hypothalamus
   • Regulates pituitary release of FSH and LH
   • Stimuates ovarian production of estrogen and progesterone
3. Menopause: cessation of cycle

Question 2

Ovarian Functions

Answer 2

1. Production of gametes ⇒ gametogenesis
   
   • Oogenesis in females
     
     • Developing gametes ⇒ oocytes
     • Ovulated gametes ⇒ ova
2. Production of steroid hormones
   
   • Estrogen and progesterone
     
     • regulates development of ova
     • produce cyclical changes to reproductive structures

Question 3

Ovarian Attachments

Answer 3

• Attached to the broad ligament via mesovarium
• Attached to uterus via ovarian ligament
  
  • remnant of embryological gubernaculum
• Attached to lateral pelvic wall via suspensory ligament of the ovary

Question 4

Ovarian Microstructure

Answer 4

• Free surface covered by simple cuboidal epithelium ⇒ germinal epithelium
• Fibrous CT layer underlying epithelium ⇒ tunica albuginea
• Composed of:
  
  • Outer cortex: cellular CT stroma
    
    • contains ovarian follicles
  • Inner medulla: loose CT with elastic fibers
    
    • contains major vasculature and nerves

Question 5

Ovarian

Blood Supply and Innervation

Answer 5

Enters and leaves via the hilus.

• Blood supplied via ovarian artery ⇒ helicine arteries
  
  • Feeds into fenestrated capillaries in the cortex
• Sympathetic and parasympathetic innervation
• Sensory afferents via T10 and T11

Question 6

Oocyte Development

Fetal Life

Answer 6

• Primordial germ cells (endoderm) migrate from yolk sac to urogenital ridges
• Oogonia increase in number by mitosis
• Peaks at 5-7 million
• Loses mitotic ability before birth
• Oogonia arrested in prophase of 1st meiotic division ⇒ called an oocyte

Question 7

Oocyte Development

Puberty

Answer 7

Starting at menarche:

• Groups of follicles undergo cyclical growth and maturation
  
  • Correlated with stages of menstrual cycle
  • One oocyte reaches maturity each cycle
• Dominant oocyte resumes meiosis
  
  • Due to pulsatile GnRH from hypothalamus
  • Oocyte + polar body
  • Becomes secondary oocyte at completion of 1st division
    
    • Arrested in metaphase of meiosis 2 unless fertilized
    • Only viable for ~ 24 hours without fertilization
    • Degenerates in uterine tube if not fertilized
• Only ~ 400 ova mature in reproductive period
  
  • Remainder undergo atresia

Question 8

Primordial Follicles

Answer 8

• Appears as early as 3rd month of fetal life
• Located in cortex just beneath the tunica albuginea
• Single layer of squamous follicle cells (stromal cells) surrounds each primary oocyte
• Oocyte cytoplasmic organelles centrally aggregate ⇒ Balbiani body

Question 9

Primary Follicles

Answer 9

Stage marks onset of follicular maturation.

Further growth dependent on gonadotrophins.

• Follicle cells become cuboidal ⇒ now called granulosa cells
  
  • Forms the membrana granulosa (stratum granulosum)
    
    • Initially forms single layer ⇒ unilaminar primary follicle
    • Later forms stratified layer ⇒ multilaminar primary follicle
• Fluid progressively accumulates between granulosa cells ⇒ liquor folliculi
• Entire follicle moves deeper into cortex
• Oocycte increases in size but remains a primary oocyte
• Zona pellucida becomes apparent by LM
  
  • layer between oocyte and granulosa cells
• Theca folliculi begins to differentiate from stromal cells
  
  • located just exterior to the membrana granulosa
  • will form two layers in 2° follicle : theca interna & theca externa

Question 10

Zona Pellucida

Answer 10

• Acidophilic, gel-like layer between oocyte and granulosa cells
  
  • rich in glycoaminoglycans and glycoproteins
• Cytoplasmic processes from oocyte and granulosa cells extend into this area
  
  • communicates via gap junctions
• Functions:
  
  • receptor for sperm via ZP3 protein
  • induces acrosome reaction
  • prevents polyspermy through protein cross-linking
  • helps oocyte travel in oviduct
  • prevents premature implantation
  • antigenic​

Question 11

Secondary Follicle

Answer 11

• Primary oocyte large and eccentrically placed
  
  • No further increases in size
• Liquor folliculi accumulates and coaleses into antrum.
  
  • Defined as a secondary follicle when this forms
  • Contains:
    
    • Hyaluronic acid and plasminogen
      
      • Breaks down cortical CT
    • Oocyte maturation inhibitor (OMI)
      
      • secreted by granulosa cells
      • inhibits completion of 1st meiotic division
    • Inhibin (folliculostatin)
      
      • inhibits FSH production
• Call-Exner bodies form between granulosa cells
  
  • Groups of granulosa cells with surrounding eosiophilic PAS+ material
  • Function unclear
  • Used as a marker for ovarian tumors with granulosa origin
• Granulosa cells near oocyte form cumulus oophorus
• Theca folliculi forms a sheath around follicle with 2 distinct layers
  
  • Theca interna:
    
    • cuboidal cells
    • characteristics of steroid producing cells
    • have LH receptors
    • secrete androstenedione (estrogen precursor)
      
      • in response to LH sitmulation
    • many fenestrated capillaries
    • s_eperated from membrana granulosa_ by basement membrane
  • Theca externa
    
    • outer layer of flat/smooth muscle like CT cells
    • contains bundles of collagen fibers
    • aids in extruding oocyte at ovulation

Question 12

Inhibins

Answer 12

Comes in two isoforms:

1. Inhibin A
   
   • produced by granulosa cells of dominant follicle
   • later made by corpus luteum
   • in pregnancy made by fetus and placenta
   • used as marker for prenatal Down’s Syndrome & ovarian tumors
2. Inhibit B
   
   • produced during follicular phase of ovary
   • made by granulosa cells of small developing follicles
   • used to predict response to IVF
   • used as a marker for ovarian tumors
   • levels decrease perimenopausally ⇒ used as marker for menopause
   • also made by Sertoli cells of testis
     
     • correlates with sperm count and testicular volume

Question 13

Graafian Follicle

Answer 13

Normally only the dominant follicle reaches this stage.

• Follicle extends the width of the cortex
  
  • produces a bulge on surface of ovary
• Antrum increases in size
  
  • fluid now includes plasminogen activator and collagenase
  • will allow oocyte to break away at ovulation
• Membrana granulosa thin except in region of cumulus oophorus
  
  • granulosa cells immediately around oocyte form the corona radiata
    
    • released with oocyte during ovulation
• Primary oocyte reenters meiosis
  
  • completes first division just before ovulation
  • results in secondary oocyte and first polar body
  • secondary oocyte now arrested in metaphase of Meiosis II
• Theca interna cells prominent
  
  • Due to LH sitmulation of steroid production

Question 14

Ovulation

Answer 14

• Decreased blood flow to ovarian surface in region overlying bulging follicle ⇒ forms macula pellucida or stigma
• Rupture
  
  • 1.5 - 2 minutes elapses between stigma formation and follicular rupture resulting in expulsion
• Release
  
  • Oocyte + cumulus oophorus + corona radiata expelled
  • Generally 1 per cycle on ~ 14th day
• Oocyte pickup
  
  • Fimbriae of oviduct move close to ovary
  • Oocyte viable for ~ 24 hours
    
    • Degenerates if not fertilized
    • Completes 2nd meiotic division if fertilized ⇒ mature ovum + second polar body

Question 15

Fertilization

Answer 15

1. Spermatozoa prenetrate corona radiata
2. Capacitation occurs
3. Acrosome reaction in spermatozoan triggered by glycoproteins of zona pellucida
   
   • Allows sperm to penetrate zona pellucida

Question 16

Prevention of Polyspermy

Answer 16

1. Depolarization of oocyte plasma membrane ⇒ “fast block”
2. Cortical reaction
   
   • contents of cortical granules of oocytes secreted
3. Zona reaction ⇒ “slow block”
   
   • triggered by cortical granule contents

Question 17

Ovarian Cycle

Follicular Phase

Answer 17

Days 1 - 14

1. FSH predominates in first 8-10 days
   
   • development of a group of follicles
   • differentiation of theca interna cells
     
     • begin production of androstenedione
   • aromatizing enzyme in granulosa cells converts androstenedione ⇒ estradiol
2. Estradiol further stimulates granulosa proliferation
   
   • Estradiol diffuses to capillary plexus in theca cell layer
3. ↑ plasma estradiol ⇒ positive feedback of pituitary ⇒ LH surge at mid-cycle
4. Dominant follicle will proceed to ovulation ~ day 14

Question 18

Ovarian Cycle

Luteal Phase

Answer 18

Days 14-28

• Begins immediately after ovulation
• Granulosa and thecal cells of ruptured follicle undergo morphological change ⇒ forms corpus luteum
  
  • Secretes estrogens and progesterone
  • Stimulates uterine endometrium to begin secretory phase
  • Maintained by LH
    
    • Degenerates as LH levels drop
  • In case of pregnancy, corpus luteum maintained by HCG

Question 19

Corpus Luteum

Formation

Answer 19

Formed from remaining granulosa and theca cells after ovulation.

• Follicle collapses ⇒ deep folds form
• Vascular bleeding from theca interna ⇒ clot for 2-3 days after ovulation ⇒ forms corpus hemorrhagicum
• Connective tissue invades cavity
• Basal lamina between granulosa and theca interna degenerates.
• Lymphatics and blood vessels invade new granulosa lutein layer.
• Cells of membrana granulosa form granulosa lutein cells
  
  • large, pale, lots of lipids, abundant SER, long microvilli
  • centrally placed within corpus luteum folds
  • produces mostly progesterone
  • also makes inhibin and relaxin
• Cells of theca interna form theca lutein cells
  
  • smaller, darker, heterochromatic nuclei, no microvilli
  • found along periphery of folds
  • produces androstenedione
• Androstenedione converted by granulosa lutein cells into estradiol

Question 20

Corpus Luteum

Functions

Answer 20

1. Regulate uterine wall for implantation
2. Inhibin ⇒ ⊖ feedback to pituitary ⇒ ↓ [FSH] ⇒ prevent follicular development
3. Relaxin early in corpus luteum of pregnancy
   
   • softens the cervix
   • inhibits uterine contractions
   • aids in angiogenesis
   • also produced by the placenta later in pregnancy

Question 21

Corpus Luteum

Fates

Answer 21

If fertilization and implantation occurs:

• Corpus luteum increases in size and becomes corpus luteum of pregnancy
• Progesterone inhibits development of other follicles
  
  • Blocks ⊕ feedback from ovary ⇒ pituitary
• Human chorionic gonadotropin (HCG)
  
  • from trophoblastic cells of chorion and later by placenta
  • stimulates development and maintenance of corpus luteum
• Corpus luteum begins to degenerate late in 1st trimester
  
  • generally does not persist beyond 6th month of gestation
  • forms large scar called corpus albicans

If fertilization does not occur:

• Corpus luteum remains active for 10-12 days until LH levels decrease
• Luteolysis = involution of CL
• Uterus produces prostaglandin F2 alpha
  
  • causes smooth muscle contractions
  • cuts off blood flow
  • results in necrosis

Question 22

Corpus Albicans

Answer 22

The corpus luteum degenerates after menstruation or pregnancy.

Corpus albicans formed.

Moves to deep cortex.

Causes visible scarring of the ovary in older females.

Question 23

Follicular Atresia

Answer 23

Degeneration of an ovarian follicle.

Can occur at any stage of follicle development.

Highly regulated process.

• apoptosis within granulosa cells
  
  • ​degenerate and sloughed into antrum of follicle
• invasion of granulosa layer by neutrophils, macrophages, and vascularized CT
• thickening of basement membrane between granulosa and theca interna can occur forming a glassy membrane
• theca interna cells become hypertrophic
• follicle collapses and CT invades follicular cavity
• macrophages move into follicle to remove debris
• atretic follicles ultimately replaced completely by collagenous tissue ⇒ corpus fibrosum

Question 24

Oviduct

Gross structure and Functions

Answer 24

Paired tubes supported by the broad ligament.

Extends from ovaries to uterus.

1. Transports ova
2. Provide environment for fertilization
3. Provide environment where embryo can develop to the morula stage

Question 25

Oviduct Wall Layers

Answer 25

The oviduct wall has three layers:

No muscularis mucosae ⇒ no submucosa.

No glands.

1. Mucosa
   
   • simple columnar epithelium containing two cell types:
     
     • ciliated cells
       
       • most common in infundibulum and ampulla
       • cilia helps transport ovum
       • favored by estrogen ⇒ most numerous in follicular phase
     • secretery (peg) cells
       
       • nonciliated cells
       • secrete nutritive material for ovum and sperm
         
         • glucose
         • bicarb ⇒ increase pH to 8.0 to loosen corona radiata
         • metabolites
         • alpha-amylase ⇒ alter sperm atigens
       • protrudes further into lumen than ciliated cells
       • favored by progesterone ⇒ most numerous in luteal phase
     • Cells hypertrophy & increase in height during follicular phase
     • Cells atrophy in luteal phase
   • Lamina Propria
2. Muscularis
   
   • composed of an inner circular and outer longitudinal layer of smooth muscle
3. Serosa
   
   • continuous with the mesosalpinx

Question 26

Oviduct Segments

Answer 26

The oviduct has 4 distinct segments:

Ovary ⇒ Uterus

1. Infundibulum
2. Ampulla
3. Isthmus
4. Intramural (interstitial) segment

Question 27

Oviduct

Infundibulum

Answer 27

• Funnel-shaped end (ostium) of the oviduct
• Located closest to the ovary
• Opens to the peritoneal cavity
• Ostium has finger-like projections called fimbriae
  
  • contains many large thin veins
    
    • become engorged with blood at ovulation
    • causes fimbrae to extend and more closely surround the ovary
  • epithelium of fimbriae continuous with and similar to that lining the lumen
  • continuous with the mesothelium of the serosa of outter surface of oviduct
• Mucosal folds of infundibulum contains many large thin walled vessels

Question 28

Oviduct

Ampulla

Answer 28

Longest segment of the oviduct (~2/3 length)

Usually the site of fertilization.

Mucosal folds are numeous, long, highly branched, and nearly fill the lumen.

Question 29

Oviduct

Isthmus

Answer 29

Narrow segment between ampulla and uterus.

Mucosal folds are fewer, shorter, and less branched.

Thicker muscularis than infundibulum or ampulla.

Question 30

Oviduct

Intramural

Answer 30

Part that passes through the uterine wall.

Has few if any mucosal folds.

Question 31

Uterus

Gross Anatomy

Answer 31

Hollow pear-shapred organ.

Lumen continuous with oviduct and vagina.

Three regions:

1. Fundus
   
   • Dome shaped region superior to site of oviduct entry
2. Body
3. Cervix
   
   • Narrow fibrous inferior portion
   • Protrudes into and opens into vagina
   • differs from the rest of the uterus histologically and physiologically

Three wall layers:

1. Endometrium ⇒ mucosa of the uterus
2. Myometrium
3. Perimetrium

Question 32

Uterine

Endometrium

Answer 32

Mucosa of the uterus.

Luminal epithelium, uterine (endometrial) glands, and stroma.

Simple columnar epithelium with mostly secretory cells and few ciliated cells.

Invaginates into stroma to form uterine glands.

Endometrium has 2 distinct layers:

1. Stratum basale
   
   • deeper part containing coiled lower portions of uterine glands
   • stroma often more cellular ⇒ basophilic
   • no cyclic changes
   • retained during menstruation
   • epithelial cells of stratum basale glands divide & migrate upwards folling menstruation
     
     • reforms the glands of stratum functionale
     • re-epithelialize denuded surface of uterus
2. Stratum functionale
   
   • lies adjacent to the lumen
   • contains upper portions of uterine glands
   • glandular morphology changes dramatically during menstrual cycle
   • shed during menstruation

Question 33

Uterine

Myometrium

Answer 33

Smooth muscle layer.

• primary function to expel fetus at parturition
• layers arranged in irregularly interlacing bundles
  
  • allows contraction of uterus
  • prevents rupture

Question 34

Uterine

Perimetrium

Answer 34

Outer connective tissue layer.

• Serosa on the fundus/body
• Adventitia around the cervix
• Laterally blends into the broad ligament
• Blood vessels from broad ligament penetrate perimetrium to supply myometrium and endometrium

Question 35

Endometrial

Blood Supply

Answer 35

Uterine artery ⇒ arcuate arteries of myometrium ⇒ radial arteries enter stratum basale

become

⇒ straight arteries (supply stratum basale)

⇒ spiral arteries i.e. helicine arteries (supply stratum functionale)

⇒ capillaries derived from spiral arteries drain into venous lakes (lacunae)

Question 36

Endometriosis

Answer 36

Tissue resembling the uterine endometrium develops in locations within pelvic cavity where it does not belong.

e.g. ovary, pelvic wall, exterior uterus

Tissue may bleed into the pelvic cavity during menstruation.

Question 37

Menstrual Cycle

Answer 37

Cyclic changes in stratum functionale correlates with maturation of ovarian follicles.

Question 38

Uterus

Proliferative Phase

Answer 38

Days 1 ⇒ 15

• Lasts until the day after ovulation
• Coincides with follicular phase of ovarian cycle
• Under estrogen influence
• Morphological characteristics:
  
  • intact epithelium
  • uterine glands lengthen via mitosis
    
    • narrow and straight or slightly wavy
  • spiral arteries begin to re-grow, reaches 2/3 way into funcitonale
  • stromal cells divide and secrete ECM components
  • entire endometrium becomes markedly thicker
• If no ovulation occurs (anovulatory cycle), endometrium remains in proliferative stage until menstruation.

Question 39

Uterus

Secretory Phase

Answer 39

Days 15-28

• Coincides with luteal phase of ovarian cycle
• Controlled by progesterone
• Early secretory phase
  
  • Glands have corkscrew appearance
  • Edema increases
• Late secretory phase
  
  • Glands have saw-toothed sacculated appearance
  • Edema decreases as fluid moves into venous lakes
  • Venous lakes larger and more prominent
  • Decidualization of stroma
    
    • Stromal cells (mesenchymal appearing) differentiate into predecidual cells
      
      • large, rounded, pale, glycogen-rich
      • becomes dicidual cells of placenta if implantation occurs
• Glycogen shift
  
  • By ~ day 17, large amount of glycogen at basal end and nucleus in the middle
  • After day 17, glycogen moves to apical end and secreted ⇒ glycogen shift
    
    • nuclei moves back to basal end of cell
  • Used to date the endometrium histologically
  • Demonstrates that ovulation has occurred
• Spiral arteries continue to elongate and span full thickness of functionale
• Glands secrete products that aid in implanation, provide nutrients, and antibacterial functions
  
  • glycogen
  • proteins
  • glycoproteins

Question 40

Uterus

Menstrual Phase

Answer 40

Day 1 ⇒ approximately day 3-5

• Constriction of spiral arteries late in secretory phase ⇒ ischemia of functionalis
• Spiral arteries relax ⇒ necrotic ends rupture
• Released blood washes away ischemic functionale ⇒ hemorrhagic discharge (menses)
• Morphological characteristics:
  
  • luminal epithelium fragmented
  • irregular surface of stroma
  • presence of RBCs in uterine lumen or extravascular in stroma
  • progressive thinning of stratum functionale as layer shed

Question 41

Implantation

Answer 41

1. Completion of fertilization produces zygote
   
   • Zygote repeatedly divides as it travels down oviduct
2. Forms solid cluster of cells ⇒ morula
3. Then forms hollow ball of cells ⇒ blastula
4. Blastula enters uterus ~ 4 days after fertilization
   
   • Begins to implant
   • Uterine wall can only support implantation between days 20-23

Question 42

Pregnant Uterus

Answer 42

• Estrogen promotes:
  
  • increased uterine wall thickness
    
    • hypertrophy and hyperplasia of smooth muscle cells
    • increased amount of CT matrix
  • increased numbers of gap junctions between smooth muscle cells
• Progesterone prevents:
  
  • premature contraction of myometrium
    
    • by keeping gap junctions closed
• Increased stretching from fetus growth causes increased spontaneous contractions
• At parturition:
  
  • Relaxin synthesized by placenta relaxes cervix
  • Oxytocin and prostaglandins promotes uterine wall contraction

Question 43

Cervix

Gross Anatomy

Answer 43

Narrow inferior portion of uterus that projects into vagina.

• Continuous with uterus at internal os
• Continuous with vagina at external os
• Cervical canal or endocervix ⇒ lumen of cervix
• Ectocervix ⇒ lies outside external os and protrudes into vagina

Question 44

Cervical Mucosa

Answer 44

• Plicae palmatae ⇒ numerous permanent folds of mucosa
• Lined by simple columnar epithelium
  
  • 95% mucus secreting cells
  • 5% ciliated cells
• Highly branched glands
• Mucus secretion changes during cycle
  
  • At ovulation
    
    • under influence of estrogen
    • increased mucus secretion
    • mucus less viscous and more stretchable
    • higher salt concentration ⇒ produces “ferning pattern” on slide
  • During secretory phase
    
    • under influence of progesterone
    • less mucus secretion
    • mucus more viscous and less stretchable
  • During pregnancy
    
    • forms thick mucus plug
      
      • acts as bacteriostatic agent

Question 45

Cervix

Squamo-Columnar Junction

Answer 45

Abrupt transition from simple columnar “cervical epithelium” to minimally keratinized stratified squamous “vaginal epithelium”.

• Location varies throughout lifetime
  
  • At birth, in the endocervix near external os
  • At puberty, migrates out to ectocervix and extends beyond external os
  • After puberty, found in the endocervix near original location
    
    • unless woman pregnant or taking birth control
• Transformation zone ⇒ the area between the furthest extent of the junction onto the ectocervix and its current location at the time of examination
  
  • common site for metaplasia, cervical carcinoma, and HPV
  • cells taken from here for PAP smears

Question 46

Nabothian Cysts

Answer 46

Enlarged clogged cervical glands.

Formed as squamo-columnar junction migrates back into the endocervix causing openings of cervical glands to become obstructed.

Normally harmless and pain-free.

Question 47

Vagina

Gross Anatomy

Answer 47

• Extends from external os of cervix to vestibule (space between labia minora)
• Hymen initially extends part way across lumen partly obstructing opening of vagina
  
  • Sex can lead to disruption

Question 48

Vaginal Wall Layers

Answer 48

1. Mucosa
   
   • Minimally keratinized stratified squamous epithelium
     
     • Numerous transverse folds ⇒ rugae
     • Epithelial cells accumulate glycogen during follicular phase
       
       • stimulated by estrogen
     • Individual cells continuously shed ⇒ holocrine secretion
       
       • increases during menstruation
     • Glycogen from shed cells metabolized to lactic acid by normal vaginal flora
       
       • lowers vaginal pH
       • protects against pathogens
   • Lacks glands ⇒ lubricated mainly by cervical mucus and transudate from blood
   • Lamina propria forms projections into epithelium
   • Large veins located deep become engorged during sexual arousal
   • No muscularis mucoae
     
     • helps distinguish vagina from esophagus
2. Muscularis
   
   • Continuous with myometrium of uterus
   • Inner circular and outer longitudinal layers
3. Adventitia
   
   • Very thick with many elastic fibers
   • Aids in wall stretching and tightening

Question 49

Placenta Development

Answer 49

Vascular organ derived from both materal and fetal tissues.

Provides nutritional and hormonal support for developing fetus.

• Blastocyst implants into the endometrial wall.
  
  • Consists of two layers:
    
    • Outer trophoblast
      
      • Forms the placenta along with the materal decidua basalis
    • Inner cell mass ⇒ forms fetus
• Throphoblast gives rise to two cell layers:
  
  • Inner layer of uninucleated cytotrophoblasts
  • Outer layer of multinucleated syncytioblasts
    
    • Produces hCG
• hCG stimulates stromal cells of stratum functionalis to differentiate into decidual cells
• Decidua basalis = layer of the decidua underneath the embryo
  
  • Forms the placenta along with the fetal trophoblast

Question 50

Decidua

Answer 50

Layers surrounding the fetus which has been derived from the uterine wall.

• Decidua basalis
  
  • endometrium between myometrium and chorion frondosum
  • contributes to placenta
• Decidua capsularis
  
  • endometrium between chorion of embryo and uterine lumen
• Decidua parietalis
  
  • endometrium lining remainder of the uterine lumen
    
    • sites other than the implanation site

Question 51

Chorion

Answer 51

Layers surrounding the fetus derived from trophoblasts.

1. Chorion frondosum
   
   • villous or “feathery” part of chorion
   • adjacent to decidua basalis
   • contributes to the placenta
2. Chorion laeve
   
   • smooth part of the chorion
   • adjacent to the decidua capsularis

Question 52

Primary Villi

Answer 52

~ Day 11 - 13 post ovulation.

• solid core of cytotrophoblast cells
• outer covering of syncytiotrophoblasts
• protrude into the lacunae

Question 53

Secondary Villi

Answer 53

Around day 16 post-ovulation.

• Primary villi ⇒ secondary villi when they develop a central core of mesoderm (mesenchyme)
• mesoderm surrounded by layer of cytotrophoblast
• cytotrophoblast covered by layer of syncytiotrophoblasts

Question 54

Tertiary Villi

Answer 54

3rd week and beyond.

• Secondary villi ⇒ tertiary villi when capillaries develop in mesodermal core
• progressive thinning of cytotrophoblast layer
• formation of the placental barrier

Question 55

Uteroplacental Circulation

Answer 55

Humans have a hemochorial placenta.

• maternal blood flows through spaces in the chorion in direct contact with chorion cells
• fetal blood flows through vessels in the chorion
• materal and fetal blood remain physically seperated
• lacunae
  
  • form within syncytiotrophoblast early in development
  • erode into maternal vessels
  • maternal blood percolates in the lacunae

Question 56

Placental Barrier

Answer 56

Complete seperation of materal and fetal blood.

Gases and nutrients diffuse across the placental barrier.

Found at the level of tertiary villi.

Includes:

• Syncytiotrophoblast
• discontinuous layer of cytotrophoblast
• basal lamina of trophoblast
• connective tissue in villus
• basal lamina of fetal capillary
• endothelium of fetal capillary

​

The thinnest placental barrier consists only of the boldfaced structures.

Basal lamina of trophoblast and endothelium can fuse to further reduce diffusion barrier.

Question 57

Early Placenta

Answer 57

Question 58

Mature Placenta

Structure

Answer 58

Fetal Component ⇒ Chorion Frondosum

1. Cytotrophoblast shell (peripheral cytotrophoblasts)
   
   • formed by cytotrophoblast cells that invade into decidua
   • outer covering of the fetal part of placenta
   • anchoring villi attached
   • interrupted by maternal blood vessels
   • fused with decidua basalis
2. Chorionic plate
   
   • makes up the fetal side of the placenta
   • layer of amniotic cells on fetal side of the plate
   • cytotrophoblast and syncytiotrophoblasts cover the side of plate facing intervillous space
   • contains large branches of umbilical arteries/veins of fetal circulation

Maternal Component ⇒ Decidua Basalis

1. Cotyledons
   
   • placenta divided into 15-25 cotyledons
   • formed by decidual partitions that grow into the maternal blood space
   • gives surface a cobblestone apperance
2. Decidual Cells
   
   • derived from endometrial stroma
     
     • transformed by interactions with blastocyst
   • large PAS+ cells WITH high content of lipid and glygogen
   • produces fibrinoid ⇒ acidophilic PAS+ material
     
     • more common on maternal side
   • secrete prolactin and prostaglandins

Question 59

Term Placenta

Answer 59

Question 60

Human Placenta

H&E

Answer 60

Question 61

Stem Villi

Answer 61

• arises directly from the chorionic plate
• contains branches of the fetal blood vessels
• various villi branch from stem villi:
  
  • those that are continuous with the decidua basalis called anchoring villi
  • those that do not fuse with the decidual basali called free villi (aka terminal or branch villi)

Question 62

Anchoring Villi

Answer 62

Branches of stem villi which are fused with the decidua basalis.

Span the distance from the chorionic plate to decidua.

Contract to mix maternal blood.

Cytotrophoblasts from anchoring villi forms the cytotrophoblast shell.

Question 63

Terminal Villi

Answer 63

Side branches of stem and anchoring villi that are not in direct contact with either the chorionic plate or decidua.

Question 64

Tertiary Villus

Structure and Function

Answer 64

May be stem, anchoring or terminal villi.

• Bathed by maternal blood in intervillous spaces
• Important in exchange between maternal and fetal blood systems
• Syncytiotrophoblast layer ⇒ outer
  
  • becomes thinned as villi mature
  • aggregates of nuclei form syncytial knots
    
    • may break off and enter maternal circulation
  • mixed characteristics of absorptive, protein secreting, and steroid producing cells
• Cytotrophoblast layer ⇒ inner
  
  • becomes greatly thinned and discontinuous as placenta matures
  • some may secrete placental LH-RH
• Hofbauer cells
  
  • present in the villous core
  • macrophage family
  • may be involved in angiogenesis

Question 65

Syncytiotrophoblasts

Answer 65

True structural syncytium.

Cells have characteristics of absorptive, protein secreting, and steroid producing cells.

• sparse microvilli (do not form brush border)
• no terminal web
• actin located near membrane
• both RER and SER prominent
• mitochondria with both tubular and shelf like cristae
• coated vesicles present
• lipid droplets
• multivesicular bodies
• shares basement membrane with some of the fetal capillaries

Question 66

Decidual Cells

Answer 66

Dervied from stromal cells of stratum functionalis under influence of hCG produced by cells of blastocyst.

• Large
• High content of lipid and glycogen
• PAS+ by LM
• May serve to protect blastocyst from immune rejection
• Secrete prolactin and prostaglandins
• Produces fibrinoid

Question 67

Placental Circulation

Answer 67

1. Maternal blood
   
   • flows via spiral arteries into intervillous spaces
     
     • initially through the lacunae of syncytiotrophoblasts
   • flows towards chorionic plate
   • percolates among the villi
2. Fetal blood
   
   • poorly oxygenated blood: fetus ⇒ placenta via paired umbilical arteries
   • oxygenated blood: placenta ⇒ fetus via single umbilical vein
   • fetal blood flows through capillaries within tertiary villi
     
     • remains seperate from maternal blood

Question 68

Umbilical Cord

Answer 68

Contains:

one umbilical vein (right vein degenerates)

two umbilical arteries

Wharton’s jelly ⇒ mucoid connective tissue

Becomes covered by the amnion ⇒ simple cuboidal epithelium.

Question 69

Placenta Functions

Answer 69

1. Absorption ⇒ mainly syncytiotrophoblasts
   
   • nutrients and metabolites
     
     • AA, FA, carbs, vitamines
   • gas exchange
     
     • O₂, CO_2​​
2. Transmission of maternal IgG from mom to fetal blood
3. Metabolite production ⇒ mainly syncytiotrophoblast
   
   • glycogen, cholesterol, FA
4. Hormone Production
   
   • steroids hormones ⇒ mainly syncytiotrophoblasts
   • peptide hormones

Question 70

Placental

Steroid Hormones

Answer 70

Largely cells of the syncytiotrophoblast.

• Estrogen
  
  • helps maintain pregnancy
  • fetal adrenal cortex involved and provides precursors
• Progesterone
  
  • helps maintain pregnancy
  • takes over for corpus leuteum

Question 71

Placental

Peptide Hormones

Answer 71

Produced by trophoblasts:

• Human Chorionic Gonadotropin (hCG)
  
  • maintains corpus luteum
  • acts like TSH by stimulating maternal thyroid production of T4
• Human Chorionic Somatomammotropin (hCS)
  
  • trophic and lactogenic
  • produced by syncytiotrophoblasts
• IGF-I and IGF-II
  
  • produced by cytotrophoblasts
  • stimulates differentiation of cytotrophoblasts
• Endothelial growth factor
  
  • early by cytotrophoblasts
  • later by syncytiotrophoblasts
  • maintains function of differentiated trophoblasts
• Leptin
  
  • produced by syncytiotrophoblasts
  • regulates materal nutrient storage relative to fetus

Produced by decidual cells:

• Relaxin
  
  • softening of cervix and pelvic ligaments prior to parturition
• Prolactin
  
  • stimulates proliferation of breast tissue and milk production
• Prostaglandin
  
  • involved in initiation of parturition

Question 72

Breast Development

Answer 72

Occurs in both males and females.

• Ectodermally derived from “milk line” tissues
• Modified apocrine sweat glands
• Under influence of maternal sex hormones
• Males with redimentary breasts throughout life
• Gynecomastia = abormally enlarged breasts in males
• Polymastia = more than two breasts
• Polythelia = extranipples

Question 73

Breast Organization

Answer 73

• Each breast with 15-20 glandular subunits ⇒ lobes
• Lobes seperated by fibrous bands of dense irregular CT
  
  • radiates from the nipple to deep fascia of thorax
  • called suspensory ligaments (of Cooper)
• Each lobe with lactiferous duct opening onto nipple
• Compound tubuloalveolar gland

Question 74

Nipple and Areola

Answer 74

Skin highly pigmented with long dermal papillae.

• Nipple
  
  • numerous smooth muscle bundles
    
    • allows for nipple erection during suckling
  • contains sebaceous glands and apocrine sweat glands
• Areola
  
  • pigmented area around nipple
  • contains sebaceous glands and apocrine sweat glands
  • contains glands of Montgomery
    
    • intermediate structure between mammary glands and apocrine sweat glands
    • produce elevations on areola
• Lactiferous sinus
  
  • dilated portion of each lactiferous duct
  • in nipple area just beneath areola

Question 75

Duct System

Mammary Gland Proper

Answer 75

• Each lobe drained into nipple by single lactiferous duct
  
  • Lactiferous sinus = dilated portion of duct near nipple
  • Sinus & proximal duct lined by stratified cuboidal epithelium
  • Stratified squamous near surface
  • Myoepithelial cells between epithelium and basement membrane
• Terminal ducts (leads to lobules) and intralobular ducts
  
  • Simple cuboidal to stratified columnar epithelium
  • Myoepithelial cells present

Question 76

Stroma and Parenchyma

Mammary Gland Proper

Answer 76

• Parenchyma (functional gland tissue)
  
  • ducts end in tubular evaginations ⇒ secretory portion of the gland
  • proliferates due to estrogen and progesterone during pregnancy
  • simple cuboidal epithelium
  • myoepithelial cells present
• Connective tissue stroma
  
  • interlobular CT
    
    • dense irregular fibroelastic CT
    • adipose
    • seperates lobules
  • intralobular CT
    
    • loose CT
    • separates glandular subunits within lobules

Question 77

Inactive

Mammary Gland

Answer 77

Glandular component sparse.

Consists largely of ducts.

Little or no secretory alveoli.

Under estrogen stimulation the cells proliferate.

Some minor cyclical changes with menstrual cycle.

Question 78

Proliferating

Mammary Gland

Answer 78

​Occurs during pregnancy.

• Proliferation and increased branching of ducts
  
  • Stimulated by estrogen
• Proliferation and development of secretory alveoli
  
  • Stimulated by high levels of progesterone, prolactin, and human chorionic somatomammotropin (hCS)
• Lobules greatly enlarge ⇒ increase in sectional profiles
• Increase in lymphocytes, plasma cells, and eosinophils in stroma
• Adipose tissue decreases
• Great variation between and within lobules

Question 79

Lactating

Mammary Gland

Answer 79

Post-partum hormonal changes release inhibition on milk production.

• decrease in lymphoid elements in CT
• increase production of lipids
• alveoli proliferate and increase in size
  
  • causes reduction of intralobular CT
• lumina of glands with secretory product
• cells with organelles for both lipid and protein secretion

Question 80

Colostrum

Answer 80

• Secreted immediately after birth
• Alkaline, yellowish secretion
• Different composition from true milk
  
  • higher protein, Vit A, and NaCl content
  • lower carbs, lipid, and K content
  • high levels of Ab

Question 81

Milk Secretion

Answer 81

Production and secretion stimulated by prolactin.

• Merocrine secretion
  
  • protein component of milk ⇒ specifically caseins
  • unusual organelles
    
    • RER for milk proteins
    • golgi for packaging
    • secretory vesicles
  • accounts for electron dense particles in lumen on EM
• Apocrine Secretion
  
  • lipid component of milk
  • lipid droplets in cytoplasm coalesce and move to apex of cell
  • apical region pinches off releasing lipid droplet into lumen

Question 82

Milk Ejection Reflex

Answer 82

• Afferent limb ⇒ neural
  
  • sensory input from suckling via afferents to hypothalamus
  • inhibits the release of prolactin inhibiting factor
• Efferent limb ⇒ hormonal
  
  • Prolactin from adenohypophysis ⇒ increased milk production
  • Oxytocin from neurohypophysis ⇒ stimulates myoepithelial cells to contract
    
    • expresses milk from alveoli and ducts

Question 83

Lactational Amenorrhea

Answer 83

Breast feeding results in high serum prolactin levels.

Suppresses production of LH.

Suppresses normal menstrual cycle.

Question 84

Breast Involution

Answer 84

Degeneration of Alveoli

• Begins at ~ 40 y/o and continues through menopause
• Due to lack of stimulation by ovarian hormones
• CT also affected
• Decrease in fibroblasts, collagen, and elastic fibers