Menstrual Cycle

Question 1

Oogenesis

Answer 1

• Process by which primordial germ cells transform into mature female gametes
• Fetus has most oogonia at 20 weeks gestational age: 6-7 million
• Enormous wave of atrophy while still a fetus –> newborn born with only 1-2 million primary oocytes
• Female down to 400,000 primary oocytes by puberty
  
  • 400 of these could one day “go down the chute” and have a chance to get fertilized
• Trigger 1: LH surge –> Meiosis 1
  
  • Causes extrusion of 1st polar body –> ovulation
• Trigger 2: Fertilization –> Meiosis 2
  
  • Causes expulsion of second polar body

Question 2

Similarities between oogenesis and spermatogenesis

Answer 2

• Female gamete referred to by variety of names – reflects sequential development of cells
• Seqeunce of meiosis is the same
• Events at a cellular level are the same
• Genetic complement of mature gamete are the same

Question 3

Differences between oogenesis and spermatogenesis

Answer 3

• Women are born with all of their eggs for life
• Timing of meiosis is different
  
  • Men = 64 days
  • Women may never complete if no fertilization
• Spermatogenesis –> 4 equivalent, mature gametes
  
  • Oogenesis only produces one
• Egg development occurs due to trigger
  
  • Spermatogenesis occurs due to wave

Question 4

Functional and histologic changes in ovarian follicle

Answer 4

• Ovarian follicle = primary functional unit of ovary
• Develops over time, passing through 2 stages (preantral and antral)
  
  • Preantral follicles: primordial follicle, primary follicle, and secondary follicle
  • Antral follicles: tertiary follicle, Graafian follicle
• Primordial follicle:

Question 5

Primordial follicle

Answer 5

• Pregranulosa cells in a sphere surrounded by basement membrane
• Most oocytes never escape this stage

Question 6

Primary follicle

Answer 6

• Contains primary oocyte
• Zona pellucida (ZP) = glycoprotein layer surrounding basement membrane of oocyte
• Granulosa cells develop

Question 7

Secondary follicle

Answer 7

• Granulosa cell layers thicken
• Theca cells start to organize
• Same primary oocyte

Question 8

Tertiary follicle

Answer 8

• Antrum in granulosa cell layer
• Organization of thecal cells into 2 layers

Question 9

Graafian follicle

Answer 9

• Antrum gets really big and fills with goodies
• Corona radiata and stalk = cumuluus oophorus form
  
  • Corona radiata - outside of ZP, it’s the stuff that’s “stuck” to ZP
  • Graafian follicle - 2 cm diameter

Question 10

Functional and histologic changes in corpus luteum

Answer 10

• Once ovulation occurs, resulting histologic unit in ovary is known as Corpus luteum
• If fertilization occurs, corpus luteum remains functional during first several weeks of pregnancy
• After that, it regresses to become the Corpus albicans
• Such regression also occurs in the absence of fertilization

Question 11

HPG axis in menstrual cycle

Answer 11

• Mid-cycle: estradiol flips from being inhibitory to excitatory for 50 hours
• Encourages LH surge to promote ovulation

Question 12

Autocrine and paracrine factors that modulate follicular development

Answer 12

• Autocrine
  
  • Granulosa cells: activin augments FSH activities
• Paracrine
  
  • Theca cells: activin suppresses androgen production, contributing to creation of estrogenic microenvironment
  • Later in follicular phase: inhibin enhances LH stimulation of androgen synthesis in theca –> providing more substrate for estrogen synthesis in granulosa cell –> estrogen peak and subsequent LH surge
• Inhibin also exerts classical endocrine functions
  
  • Inhibin-B (secreted by granulosa cell) suppresses FSH secretion by pituitary to ensure dominance of single follicle

Question 13

Emergence of dominant follicle

Answer 13

• Primary factor for differentiation: local hormonal milieu
  
  • Dominant follicle has more estrogenic microenvironment
  • Better blood supply –> increases delivery of FSH to follicle
• By day 9 of cycle, dominant follicle has more FSH receptors, greater rate of granulosa cell proliferation, more aromatase activity, and more estrogen production
• Inhibin production from dominant follicle also rises
• Rising E2 and inhibin concentrations exert negative feedback on subsequent FSH secretion –> widening gap between itself and other non-dominant follicles in cohort
• Remaining follicles more androgenic
  
  • Less able to convert androgens from theca cells into estrogens –> androstenedione accumulates –> follicles regress

Question 14

2-cell theory of sex steroid production

Answer 14

• Granulosa cells respond to **FSH **and make Estradiol
• In response to LH secretion, theca cells produce progesterone and adrogens
  
  • but lack aromatase and therefore capacity to make estrogens
• Androstenedione from theca cells must diffuse into nearby granulosa cells for estrogen to be produced
• Granulosa cells (which do have aromatase) then convert androstenedione into estradiol
• Granulosa cells lack enzymes to convert progesterone into androgens
  
  • Therefore, progesterone from granulosa cells must diffuse to theca cells to be converted into androstenedione and then diffuse back to granulosa cells to be converted into estradiol

Question 15

Histologic layers of endometrium

Answer 15

• Endometrium/uterine lining = simple columnar epithelium that forms tubular glands supported by thick vascular stroma
• Both glands and stroma undergo extensive changes during menstrual cycle
• Endometrium further subdivided into three distinct layers:
  
  • Stratum basalis
  • Stratum functionalis
  • Stratum spongiosum
  • Stratum compactum
• Overall:
  
  • Perimetrium –> myometrium –> basalis –> spongiosum –> compactum –> lumen

Question 16

Stratum basalis

Answer 16

• Deepest layer
• Sits immediately adjacent to myometrium and does not change appreciably during menstrual cycle
• Permanent stromal tissue of endometrium, contains basis of endometrial glands
• Contains stem cells

Question 17

Stratum functionalis

Answer 17

• Shed during menstruation
• When progesterone levels drop off - functional layer subject to ischemia –> dies
• Subdivided into:
  
  • Stratum spongiosum
    
    • Thick intermediate layer between basalis and compactum
    • Name derived from spongy appearance
  • Stratum compactum
    
    • Superficial layer that sits on top of spongiosum

Question 18

Spiral vs. straight arteries of endometrium

Answer 18

• Blood supply to endometrium = branches of uterine arteries which pass into myometrium
• Divided into 2 different types: straight and spiral
• Straight arteries
  
  • Feed stromal layer of endometrium
  • Do not infiltrate endometrium very deeply
• Spiral arteries
  
  • Pass through basal layer and into stratum functionalis
  • Hormonally sensitive
  • Constrict in response to hormone shifts
  • Causes stratum functionalis to become ischemic and shed

Question 19

Proliferative phase of endometrial cycle

Answer 19

• AKA “first half” of menstrual cycle
• Name derived from functional changes that occur in endometrium in response to ovarian estrogen
• Endometrial stroma proliferates & becomes thicker, highly vascular
• Tubular glands of stratum compactum that invaginate from endometrial surface elongate, straighten, then progressively become more coiled

Question 20

Secretory phase of endometrial cycle

Answer 20

• Occurs in response to high levels of progesterone secreted by corpus luteum
• Endometrial glands become more torturous, stroma becomes more edematous
• Glands secrete substance rich in glycogen, capable of sustaining conceptus until placentation can occur