Female Repro Histo and Physio Flashcards

1
Q

Pituitary- Ovary Cross-talk

A
  1. Corpus luteum dies, E and P levels fall.
  2. Pituitary responds to falling E and P by increasing FSH secretion
  3. FSH recruit a cohort of large antral follicles to enter rapid growth phase. Follicles secrete low amounts of E and inhibin.
  4. E and inhibin negatively feed back on FSH.
  5. Declining FSH levels progressively cause atresia of all but 1 follicle– leading to selection of dominant follicle, which produces high levels of E.
  6. High E has positive feedback on gonadotropes– LG (and some FSH) surges.
  7. LH surge induces metabolic maturation, ovulation, and luteinization. The corpus luteum produces high P, along with E and inhibin.
  8. High P, E, and inhibin negatively feed back on LH and FSH, returning them to basal levels.
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2
Q

pulsatile GnRH release

A

Days 15-0 : 1 pulse per hour–> high LH, low FSH
Days 0-15: 1 pluse / 3 hours–> meeting in the middle
back to 1 pulse/ hour

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3
Q

Ovary structure: medulla

A

Central portion
Loose connective tissue
Blood vessels, lymphatics and nerves

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4
Q

Ovary structure: cortex

A

Peripheral portion
Contains ovarian follicles
Smooth muscle fibers
Highly cellular connective tissue

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5
Q

Ovarian follicle maturation

A

ovarian phases

follicular phase
- lasts about 14 days
- only 1 ovary involved in a single menstural cycle
- during follicular phase: FSH stimulates cohort of follicles to mature, follicles produce estradiol, level peaks just prior to ovulation
mid-cycle surge of luteinizing hormone (LH) thru estradiol-mediated mechanism necessary to stimulate ovulation

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6
Q

Histology of ovarian follicles

A

Distributed throughout cortex
Size indicates the developmental state of the oocyte
Contain:
Ooctyes, Follicular cells (Change in shape and number during follicle development)

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7
Q

Histology of primordial follicle

A

Earliest stage
Arrested at prophase of the first meiotic division during fetal development
Just beneath the tunica albuginea
Appearance:
Primary oocyte
–Eccentric nucleus with dispersed chromatin and prominent nucleoli
–Single layer of squamous follicular cells
–Surrounded by a basal lamina

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8
Q

Histology of primary follicle

A

Development of follicular cells
Appearance:
Unilaminar primary follicle
- Primary oocyte (Enlarges, Begins to secrete glycoproteins that will assemble into an extracellular coat (zona pellucida, necessary for fertilization))
-A single layer of cuboidal follicular cells (Hypertrophy)

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9
Q

Multilaminar primary follicle

A

Primary oocyte
Stratum granulosum
- Several layers of cuboidal to columnar follicular cells
(Hyperplasia, Now called granulosa cells, Avascular)

Zona pellucida
(Glassy membrane, Mature glycoprotein coat)

Theca folliculi
(External to the basal lamina, Stromal (CT) cells)

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10
Q

Secondary follicle (antral follicle)

A

Accumulation of follicular fluid
Appearance:
- Primary oocyte
(Growth now inhibited by granulosa cells)

  • Liquor folliculi in the intracellular spaces of follicular cells (Eventually form a single fluid filled antrum)
  • Zona pellucida (Well developed)
  • Theca interna (Steroid responsive and steroid producing stromal cells, Highly vascular)
  • Theca externa (Smooth muscle cells)
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11
Q

Graafian folicle

A

Mature follicle
Large, covers full thickness of cortex and creates bulge on surface of ovary
Follicular fluid forms a large central antrum
Appearance:
- Primary oocyte (Eccentric)
- Antrum (Primary feature)
- Cumulus oophorus (Thickened mound of granulosa cells, Will detach prior to ovulation)
- Corona radiata (Granulosa cells that immediately surround oocyte and remain after ovulation, Will become a single layer prior to ovulation)

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12
Q

Ovulation

A

Mid-cycle surge of LH leads to ovulation. Proteases from fibroblasts degrade collagen fibers of the tunica albuginea and theca externa.

The mural granulosa cell layer fols soon after ovulation.

The basement membrane breaks down, blood vessesl from the theca interna invade the folding granulosa cell layer, and the antral cavity is filled with blood. (corpous hemorrhagicum).

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13
Q

oocyte activities

A

at ovulation primary oocyte completes 1st meiotic division
produces 2° oocyte & polar body (with an unequal division of cytoplasm)

2° oocyte receives:
nearly all cytoplasm
half of chromosomes

2° oocyte is haploid with 23 css (but still 2N DNA)

after ovulation oocyte "picked up" by fimbriae 	
enters infundibuium
transported to uterus by:		
peristalsis (primary motive force)		
ciliary action

oocyte enters 2nd meiotic division,
BUT suspended in metaphase II
stays in metaphase II until fertilization

if fertilized, secondary oocyte divides, produces:
another polar body
ovum (haploid, 1N DNA)

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14
Q

Ovulation & follicular atresia

A

ovulation vs. atresia
ovulation usually produces single fertilizable oocyte BUT, cohort of follicles forms under FSH influence
dominant follicle emerges 1 week before ovulation mechanism selecting dominant follicle unclear remaining follicles become atretic

in follicular atresia: oocyte dies, and antrum collapses granulosa cells stop dividing, detach from basal lamina during atresia some theca interna cells persist make up “interstitial glands”, which secrete androgens thru-out life

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15
Q

Corpus Luteum (histology)

A

At ovulation, the follicle collapses and transforms into the luteal gland (luteinization)

Breakdown of basement membrane

Invasion of blood vessels (Corpus hemorrhagicum: Fibrin clot in former antral space)

Transformation of cells

  • Follicular (granulosa) lutein cells (Large, vacuolated, Centrally located, Form a thick folded layer around the former follicular cavity)
  • Theca lutein cells (Smaller, vacuolated, Peripherally located, Cytoplasm more purple)

If fertilization and implantation occur, it increases in size

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16
Q

Corpus luteum (physiology)

A

after ovulation LH still secreted by pituitary
luteal phase of ovarian cycle (14 days)
follicle undergoes transformation
becomes corpus luteum under effects of LH
persistence of corpus luteum depends on LH

granulosa cells hypertrophy
(now called granulosa lutein cells)
characteristic steroid secreting cells

thecal cells surround granulosa lutein cells
now called theca lutein cells
secrete estrogen and progesterone
receptor synthesis promoted by estradiol
estradiol feeds back on pituitary to inhibit LH secretion
by day 25 LH levels too low to support steroidogenesis
menstruation follows

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17
Q

Corpus albicans

A

Scar formed from regression of the corpus lutein (luteolysis) after pregnancy or menstruation
Involution
- Cells decrease in size and undergo autolysis
White scar
- Deposition of intracellular hyaline material
- Disappears after several months

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18
Q

Atretic follicles

A

At any one time, several follicles initiate maturation but only one or two complete it
The remainder degenerate or undergo atresia

Appearance:

  • Thick, folded or collapsed follicle
  • Intact zona pellucida
  • One or more layers of follicular cells
  • Remnants of degenerated oocyte
  • Macrophages
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19
Q

Oviduct function

A

oviducts (uterine tube or Fallopian tube)
function:
fertilization usually occurs here
most commonly in ampulla
conveys oocyte to uterus
implantation, development & growth occur in uterus

20
Q

Fallopian tube (Uterine tube or oviduct) histology

A
Resembles visceral organs in structure (but without submucosa)
Serosa (peritoneum)
- Outermost, CT
- Contains vasculature
Muscular layer (muscularis)
- Inner, thick circular layer
- Outer, thin longitudinal layer
- Peristalsis
Lamina propria
Mucosa
- Simple columnar epithelium
Fimbria
In the infundibulum
Mucosal folds
In ampulla and isthmus
Ciliated
More numerous in infundibulum and ampulla (closer to ovary) 
Non-ciliated cells
Secretory
21
Q

Hormone effects- oviduct

A

estrogen increases: endosalpinx epithelial size, blood flow to lamina propria, oviduct specific glycoproteins, ciliogenesis, mucus, muscular tone of the isthmus

progesterion decreases epithelial size and mucus, increases deciliation, relaxes muscular tone

22
Q

Uterine Cycle

A
aka endometrial cycle, menstrual cycle	described as 28 days in length (but is variable)
divided into:			
1.	menstrual phase			
2.	resurfacing phase			
3.	proliferative phase			
4.	secretory phase			
5.	ischemic phase
23
Q

Hormone effects uterus

A

Proliferative (ovarian follicular phase)

  • Reepithelialization of the basal layer
  • Estrogen drives cellular proliferation
  • Induces expression of progesterone receptors

Secretory (ovarian luteal phase)

  • Inhibition of endometrial growth
  • Stimulation of uterine glands
  • Changes to adhesivity of surface epithelium
  • Opposes proliferative effect of estrogen

Menstrual (occurs upon demise of the corpus luteum)

  • Coincides with early follicular phase
  • Upregulates MMPs
  • Upregulation of COX-2 (results in PGF2)
24
Q

Endometrium overview

A

Undergoes cyclical changes each month throughout reproductive life
1 mm to 6 mm thick
Two zones:
1.) Stratum functionale
- Thickest portion
- Sloughed during mentstration
- Divided into: Stratum spongiosum
(Broad intermediate layer, spongy appearance) and Stratum compactum
(Thin superficial layer, stromal appearance)

  1. ) Stratum basale
    - Retained during menstration
    - Source for the regeneration of the stratum functionale
25
Q

Endometrium histology

A
Endometrial surface
- Simple columnar epithelial lining
Ciliated
Endometrial stroma
- The lamina propria
Endometrial glands
- Simple tubular
26
Q

Endometrium arterial supply

A
Myometrium
- Branches of uterine arteries
Stratum basale
- Straight arteries
Stratum functionale
- Spiral arteries (Coiled, long, thick-walled, Responsive to hormones)
27
Q

Three phases of endometrium

A

menstrual
proliferative
secretory (progestational)

28
Q

Proliferative endometrium

A

9 days (5 through 14)
Mitosis and migration of epithelial cells and stromal cells
- Stimulated by estrogen from maturing follicle
Early proliferative period
- Glands short, straight, narrow
- Lamina propria is compact
Midproliferative period
- Glands are longer and straight due to epithelial migration
- Lamina propria is slightly edematous
Late proliferative period
- Glands grow rapidly and become tortuous
- Lamina propria is more edematous

29
Q

Secretory endometrium

A

13-14 days (14 through 28)
Begins when ovulation occurs
Glands secrete glycoproteins
- Become irregular and significantly coiled
- Epithelium accumulates glycogen in basal portion (May be visible as a gap at basal surface of epithelium, Nucleus displaced centrally)
Blood vessels increase in length
Lamina propria becomes excessively edematous

30
Q

Ischemic Period

A

Decrease in circulating hormone levels eventually leads to spiral artery contraction
The resultant ischemia leads to necrosis of the stratum functionale

31
Q

Implantation

A

Delays decline of the endometrium until after parturition

Corpus luteum of pregnancy

  • Increases in size if implantation occurs (Fills most of ovary in early pregnancy)
  • Declines gradually after 8 weeks when placenta takes over hormone production
  • -> To corpus albicans

Decidua
Produced by a morphological change in the endometrium (decidualization)
All but the stratum basalis
Stromal cells
Differentiation into rounded decidual cells
Uterine glands
Initially enlarge and become more coiled
Eventually become thin and flattened due to growing fetus

32
Q

Cervix

A

Lower extension of the uterus

Different endometrium

33
Q

Three zones of cervix mucous membranes

A

Endocervix, Ectocervix, transformational zone

34
Q

Endocervix

A

Extends from uterine cavity to external os of cervix
Mucous-secreting columnar epithelium
- Mucous production regulated by estrogens
Tubular glands extend into lamina propria

35
Q

Ectocervix

A

Continuous with vaginal epithelium

Stratified squamous epithelium

36
Q

Transformational zone

A

Transition from columnar to squamous epithelium (squamocolumnar junction)
Reproductive age
- Just outside of external os
Pre-puberty and post-menopause
- Within cervical canal
95% of cervical epithelial neoplasia arise here

37
Q

Cervical cytology: pap smear: goal

A

Goal is to identify dysplastic cells before they progress into a carcinoma in situ (irreversible)

  • Metaplasia
    Reversible change in which one cell type is replaced by another
    Occurs normally in the transformational zone during reproductive age
    Can occur due to chronic inflammation from infection
  • Dysplasia
    Reversible change in which a cell type is replaced by an abnormal cell
    Occurs due to chronic inflammation from high risk HPV
38
Q

pap smear procedure

A

Scrape or brush cells from the transformational zone
H & E with additional dyes and alcohols

Normal Appearance:

  • Surface cells (cells that would be sloughed)
  • –Squamous
  • –Pink appearance due to accumulated keratin
  • –Contracted nuclei
  • Deeper cells
  • –Squamous
  • –Blue/green cytoplasm
  • –Less keratin accumulation
  • –Slightly larger nuclei
39
Q

Vagina

A

Fibromuscular tube or sheath

3 layers: inner mucosa, intermediate muscular layer, outer adventitia

40
Q

Inner mucosa of the vagina

A

Stratified squamous epithelium with lamina propria
No glands in the wall of the vagina
Glands located in vestibule
Hormone-responsive differentiation and proliferation occurs near lamina propria

41
Q

Intermediate muscular layer of the vagina

A

Inner circular and outer longitudinal

42
Q

Outer adventitia of the vagina

A

Inner dense CT and outer loose CT

43
Q

Hormone effects: cervix

A

Estrogen
stimulates production of a thin, watery and slightly alkaline mucus

Progesterone
stimulates production of a scant, viscous, slightly acidic mucus

44
Q

Hormone effects: vagina

A

Estrogen
stimulates proliferation of the vaginal epithelium
increases glycogen content

Progesterone
increases the desquamation of the epithelial cells

Glycogen
metabolized to lactic acid by commensal lactobacilli
maintains an acidic environment and prevents infections

45
Q

Systemic Estrogen/ Progesterone Effects

A
Bone
estrogens:
promotes closure of epiphyseal plates 
is an anabolic and calciotropic hormone
Liver
estrogens:
increase LDL receptor
HDL levels
cortisol binding-protein
thyroid hormone-binding protein 
sex hormone-binding protein

Cardiovascular System
estrogens: vasodilation through NO synthesis

Central Nervous System

estrogens: appear to be neuroprotective
progesterone: regulate set-point for thermoregulation

46
Q

Uterus histology

A

Resembles visceral organ structure

Endometrium
Inner mucosa
Undergoes cyclical changes

Myometrium
Thick, smooth muscle layer
Undergoes hypertrophic changes during pregnancy
Abundant vasculature
Smooth muscle fibers arranged circularly, longitudinally and obliquely
Uterine fibroids
Exist in myometrium as whorls of smooth muscle fibers

Perimetrium
Outer serous layer