The Red Plague aka Menstrual cycle

Question 1

Describe oogenesis

Answer 1

• Oocytes take 12-50 years to progress through meiotic division
• maternal/paternal homologous chromosomes pair up, undergo recombination and are arrested in prophase I as primary oocytes (46, 4N) until puberty.
• At puberty (with each cycle), the reduction division is completed due to LH surge to give you a secondary oocyte (23, 2N) and a polar body. Secondary oocyte arrested in meiosis II (metaphase), which is completed only if fertilization occurs – fertilized ovum and 2nd polar body (23C, 1N)

Question 2

Name/describe functional and histologic changes in ovarian follicle and corpus luteum

Answer 2

• oocyte develops in ovarian follicle– primary functional unit of ovary
  (primordial follicle – primary follicle – secondary follicle – tertiary follicle – graafian follicle)
• Preantral folicles = primordial through secondary
• Antral follicles: tertiary/graafian
• 10-30 follicles start maturing each day. Cohort selected for further maturation start process about 3 days before menses of prior month. One dominant follicle will dominate and be released during ovulation. Once ovulation occurs, leftover follicle becomes corpus luteum, secreting progesterone during the first few weeks of pregnancy, then regresses to corpus albicans
• if no pregnancy, still progresses to corpus albicans

Question 3

Name and describe the structure, functions, and mechanisms of action of the hormones involved in the hypothalamic-pituitary-gonadal axis in women

Answer 3

• Pulsatile secretion of GnRH by hypothalamus triggers release of FSH and LH from pituitary.
• FSH acts on granulosa cells in ovary to produce estrogen from androgens using aromatase
• LH acts on theca cells to produce androgens (lack aromatase so have to send it over to Granulosa cells)
• Production of estrogen/progesterone feeds back to inhibit release of LH/FSH from pituitary

Question 4

what causes LH surge

Answer 4

High estrogen levels above 200 for over 50 hrs causes a switch from being inhibitory to being stimulatory for release of LH from pituitary

Question 5

How many gametes to females have throughout life

Answer 5

• Females: produce gametes in utero, but most undergo atresia. By 20 weeks gestation we have 6-7 million. 1-2 million oocytes left at birth– about 400,000 left at puberty and only 1 released per month
• Males undergo both rounds of division in 64 days

Question 6

Main similarities/ differences between female/male gametogenessis

Answer 6

SAME:
- sequence, events, genetic equivalent of final gamete

DIFF

• time to make gametes (years vs months)
• only 1 mature gamete produced in F vs 4 equivalents in M

Question 7

difference between polar bodies produced in oogenesis during 1st and 2nd division

Answer 7

• Polar body from first division has 23 C, 2N and can degenerate or divide again
• Polar body from 2nd division has 23 chromosomes and non-duplicated DNA

Question 8

Describe the phases of menstrual cycle

Answer 8

• can be divided into phases based on ovarian activity/histology or basis of endometrial activity/histology

Ovarian function phases:

• Follicular Phase
• Luteal phase (most consistent)

Endometrial activty phases:

• Menstrual phase
• proliferative phase
• secretory phase

Question 9

What factors decide which follicle is superior

Answer 9

1) do they contain oocyte vs not (corpus luteum)
2) maturation of egg (Primary vs secondary)
3) degree of organizaiton in surrounding G and T cells
4) sensitivity of adjacent stromal cells to FSH/LH (winner will have more receptors)
5) amount of estrogen/progesterone they produce (winner does more)
6) amount of blood flow to them (winner has more)

Question 10

FSH effects on ovary

Answer 10

• cell division/proliferation
• increased receptors
• increased LDL receptors,
• induces production of aromatase
• estrogen/progesterone increase,
• protein production

Question 11

how does maturation of oocyte correlate to maturing follicle

Answer 11

Names assigned to follicles NOT same as oocyte within them.

• primary oocyte can be in primordial, primary, secondary, tertiary or even graafian follicle
• secondary oocyte in graafian follicle just before ovulation

Question 12

primary factor differentiating dominant follicle from cohort

Answer 12

local hormones

• dominant follicle has more estrogenic microenvironment due to blood supply increasing FSH delivery. by 9th day, already has 2x blood flow than other follicles. Also has increased FSH receptors, greater rate of granulosa cell proliferation, more aromatase activity and thus more estrogen
• Inhibin production also rises
• Estrogen/inhibit feed back to inhibit subsequent FSH secretion to widen gap between itself/other loser follicles

Question 13

What happens to non-dominant follicles

Answer 13

They are more androgenic. At low concentrations, weak androgens (androstenedione) from T cells diffuse to G cells to become estradiol via aromatase
- at high concentrations, weak androgens preferentially converted to DHT by 5-alpha-reductase. More potent androgen inhibits LH receptor formation and aromatase. Less likely to make estrogen– androstenedione builds up and follicle regresses

Question 14

Primordial follicles

Answer 14

• Preantral
• most follicles never leave this state
• begin to occur in female fetus around 6 months. Consist of primary oocyte with layer of pregranulosa cells surrounded by basement membrane - may play supporting role in development of dominant follicle each cycle via steroid hormone production

Question 15

Primary Follicle

Answer 15

• primordial follicle destined to ovulate; pre-antral
• larger oocyte surrounded by zona pelucida (glycoprotein coat facilitating sperm attachmet/fertilization of secondary oocyte). ZP surrounded by single layer of cuboidal granulosa cells and basement membrane

Question 16

Secondary follicle

Answer 16

• contains primary oocyte, zona pellucida, several layers of cuboidal granulosa cells, basement membrane
• adjacent stroma differentiates into theca cells, and vascular supply to area increases.
• Granulosa cell acquire receptors for FSH, androgen, and estrogen and become hormonally active
• Theca cells develop LH receptors and start producing steroids

Question 17

Tertiary follicle

Answer 17

• Antral
• contains primary oocyte, zona pellucida, granuosa cell layers
• FSH/estradiol cause granulosa cells to proliferate and acquire LH receptors. Fluid-filled space (antrum) develops in granulosa layer. Granulosa cell layer surrounded by basement membrane, followed by theca interna and theca externa
• Antral fluid = components from plasma exudate, follicular secretions (estradiol, progesterone, androgens, inhibin, activin, FSH, LH); play role in follicle development, ovulation, modulation of hormonal responses

Question 18

Graffian follicle

Answer 18

• Antrum enlarges– primary oocyte, zona pellucida and inner halo of granulosa cell (CORONA RADIATA) become enveloped by antral fluid. This structure is attached to remaining granulosa cells via a stalk (CUMULUS OOPHORUS)
• before ovulation, cumulus oophorus breaks down adn the oocyte, zona pellucida, and cumumus float within the enlarging follicle which eventually ruptures

Question 19

What initiates ovulation

Answer 19

estradiol peak followed by LH surge
- extrusion of oocyte mediated by weakening follicular wall as a result of collagenase, plasmin, and prostaglandin activity and smooth muscle contractions within thecal layer of follicle

Question 20

Corpus luteum

Answer 20

remaining shell of dominant follicle after ovulation

• consists of granulosa cells and theca cells
• VERY VASCULAR to deliver gonadotropin to stimulate progesterone/estrogen secretion and delivers LDL cholesterol
• some estrogen secretion

Question 21

what happens to ovulated follicle

Answer 21

• Fertilization occurs, hCG secreted by conceptus to maintain corpusluteum and progesterone secretion for ~9 weeks until placenta produces progesterone on its own (hCG shares alpha subunit with LH)
• • No fertilization: no hCG secretion so corpus luteum regresses about 11 days post ovulation. Reduced progesterone secretion – disintegration and sloughing of endometrium. Corpus luteum fibroses to become corpus albicans

Question 22

Hypothalamus and pituitary hormone secretion

Answer 22

• pulsatile GnRH secretion, but amplitude/frequency change
• At beginning of follicular phase, LH/FSH levels equal.
• GnRH stimulates transcription of genes for LH/FSH alpha unit. Occupied GnRH receptors internalized/recycled

Question 23

General hormone progression during menstrual cycle

Answer 23

• ↑ Estrogen
• LH surge onset (about 36 h before ovulation–basis for predictor kits)
• LH peak (14-24 hrs after estradiol peak)- DAY 14
• completion of meiosis I with extrusion of first polar body
• Ovulation (10-12 hrs after LH peak)- DAY 15
• oocyte to ampulla of fallopian tube (2-3 min)
• Progesterone (from corpus luteum)
• Progesterone levels fall if no fertilization
• Menstruation (via apoptosis of endometrial cells)

Question 24

Dysmenorrhea

Answer 24

pain with menses; often assd with endometriosis

Question 25

oligomenorrhea

Answer 25

> 35 day cycle

Question 26

polymenorrhea

Question 27

Metorrhagia

Answer 27

frequent of irregular menstruation

Question 28

Menorrhagia

Answer 28

heavy menstrual bleeding; >80 mL blood loss or >7 days menses

Question 29

Menometrorrhagia

Answer 29

heavy, irregular menstruation

Question 30

endometrial structure

Answer 30

• endometrium= simple columnar forming tubular glands with thick stroma
• 3 layers: stratum basalis (deepest), stratum spongiosum, stratum compactum
• Stratum functionalis (top layer)further divided into stratum spongiosum and compactum; is shed during menstruation

Spongiosum= thick intermediate layer
Compactum - superficial layer

Question 31

Blood suppliy to endometrium

Answer 31

consists of uterine artery branches passing into myometrium

• Straight arteries– feed stromal layer–don’t infiltrate endometrium deeply
• Spiral arteries- pass through basal layer and into stratum functionalis; hormonally sensitive and constrict in response to hormonal shifts–causes ischemia and shedding

Question 32

endometrial phases of menstrual cycle

Answer 32

Proliferative phase: first half of cycle due to functional changes from estrogen. Stroma proliferates, gets thicker and highly vascular. Tubular glands elongate and become more coiled

Secretory Phase: in response to high progesterone from corpus luteum; endometrial glands become more tortuous and stroma more edematous; glands secrete substance rich in glycogen–can sustain conceptus until placentation

Menstrual- endometrial ischemia – shedding of stratum functionalis (meses). Corpus luteum degenerates so estrogen/progesterone levels fall. Spiral arteries feedign stratum functionalis constrict–ischemia–blood leaks into endometrial layer–stromal cells disaggregate and endometrial glands collapse

menses= blood, necrotic epithelium, necrotic stroma, inflammatory cells and fibrin deposits

Question 33

action of FSH

Answer 33

• stimulate granulosa proliferation, increase FHS/LH receptors on G cell, stimulate estrogen production, produce autocrine-paracrine factors (activin/inhibin)
• activin augments FSH activities and suppresses androgen production in theca cells–creates estrogenic microenvironment

Question 34

Inhibin action

Answer 34

Later in follicular phase– it enhances LH stimulation of androgen synthesis in theca cells– more substrate for estrogen production
- Inhibin also suppresses FSH secretion from pituitary to ensure dominance of single follicle

Question 35

Hormonal feedback mechanisms

Answer 35

Estradiol feeds back to inhibit hypothalamus and pituitary, except in mid-follicular phase when over 200 pg/ml x 50 hrs) when it converts to positive feedback to cause LH surge that induces ovulation. LH surge about 48 hrs

Progesterone stimulatory at lower concentrations (follicular phase), inhibitory at higher concentrations (luteal). Facilitates positive feedback from estrogen midcycle (needs estrogen priming)

• at higher levels, P inhibits GnRH secretion and thus folliculogenesis. Decreased GnRH–lower LH/FSH–E and P fall. With estrogen fall, FSH begin to rise before onset of mesnses