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
Endometrium histology
``` Endometrial surface - Simple columnar epithelial lining Ciliated Endometrial stroma - The lamina propria Endometrial glands - Simple tubular ```
26
Endometrium arterial supply
``` Myometrium - Branches of uterine arteries Stratum basale - Straight arteries Stratum functionale - Spiral arteries (Coiled, long, thick-walled, Responsive to hormones) ```
27
Three phases of endometrium
menstrual proliferative secretory (progestational)
28
Proliferative endometrium
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
Secretory endometrium
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
Ischemic Period
Decrease in circulating hormone levels eventually leads to spiral artery contraction The resultant ischemia leads to necrosis of the stratum functionale
31
Implantation
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
Cervix
Lower extension of the uterus | Different endometrium
33
Three zones of cervix mucous membranes
Endocervix, Ectocervix, transformational zone
34
Endocervix
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
Ectocervix
Continuous with vaginal epithelium | Stratified squamous epithelium
36
Transformational zone
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
Cervical cytology: pap smear: goal
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
pap smear procedure
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
Vagina
Fibromuscular tube or sheath 3 layers: inner mucosa, intermediate muscular layer, outer adventitia
40
Inner mucosa of the vagina
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
Intermediate muscular layer of the vagina
Inner circular and outer longitudinal
42
Outer adventitia of the vagina
Inner dense CT and outer loose CT
43
Hormone effects: cervix
Estrogen stimulates production of a thin, watery and slightly alkaline mucus Progesterone stimulates production of a scant, viscous, slightly acidic mucus
44
Hormone effects: vagina
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
Systemic Estrogen/ Progesterone Effects
``` 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
Uterus histology
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