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Ovary
- sits in the pelvic cavity
- covered by a visceral peritoneum (mesothelium, cuboidal cells)
- deep to the epithelium is a dense CT capsule called the Tunica Albuginea
 - deep to that is the outer cortex which will contain follicles at different stages
- within the follicles are primary or 2ndary oocytes & supporting cells
- the medulla doesn't contain any type of follicles, just has stroma & BVs (esp. a highly coiled artery)
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Where do most ovarian tumors arise?
- mesothelial covering, aka the visceral peritoneum
- it's the site of 70% of ovarian tumors
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Ovarian Cortex
- can see lots of follicles at many different stages
- most peripheral: primordial follicles
- as they develop they move inward
- most will die, only 1 will fully mature
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Follicle Cycle
- have 6-700,000 primordial follicles at birth
- each month a few will begin to develop into primary follicles
- when primary follicles develop an antrum (space), they're called Vesicular follicles
- mature Vesicular follicles are called Graffian follicles (larger antrum)
- following ovulation, what's left of the follicle becomes a corpus luteum of menstruation or pregnancy
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Primordial Follicle
- the earliest stage of follicle development
- each contains a primary oöcyte surrounded by one layer of squamous follicular (granulosa) cells resting inside a thin basal lamina
- the internal primary oöcyte has a large, vesicular nucleus w/ a large nucleolus
- it's arrested in the diplotene stage of prophase of meiosis I
- this means it contains duplicated chromosomes (4n DNA)
- crossing-over has already occurred, meaning genetic sequences differ from parent

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Why isn't a primordial follicle considered foreign?
- even though the gametes are “foreign” because they have different DNA than the parent cells, this event occurs prior to development of immunocompetence
- therefore gametes are not attacked by the host immune system, they're considered "self" & don't need to be kept separate from the blood supply (unlike in testes)
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Weird Things in Primordial Follicles
- Balbiani Body: collection of golgi membranes in the oocyte; will disperse later
- Annluate Lamellae: stacks of nuclear membrane (darkenings = nuclear pores); role in oocyte development = unclear

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Primary (Early) Follicles
- starting at puberty & at the beginning of every future menstrual cycle chosen follicles (aka those with the most FSH receptors on their surface) begin to mature
- 1st thing to change is that the flattened follicular (granulosa) cells around the oocyte become cuboidal
- this characterizes a unilaminar primary follicle
- follicular cells still sit on a basal lamina
- zona pellucida starts to develop between the follicular cells & oocyte
- these oocytes/follicles becomes larger (esp. in comparison to primordial follicles)

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Primary (Late, Multilaminar) Follicles
- cuboidal follicular cells have now proliferated, called granulosa cells (these may represent a pseudostratified epithelium but look like several layers of follicular cells)
- has a thicker zona pellucida
- oocyte is larger
- cellular stroma immediately around the follicle differentiates into theca cells
- follicle & oocyte are still enclosed by a complete basal lamina separating them from the theca cells

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How can granulosa cells & an oocyte communicate?
- granulosa cells have microvilli projections that extend through the zona pellucida to the oocyte
- the oocyte also has processes that extend through the ZP to granulosa cells
- there are also gap junctional connections between the 2
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Secondary (Antral) Follicle
- antral refers to the fact that they have a fluid filled region within the field of granulosa cells
- that antrum will grow
- granulosa cells exist at the periphery of the follicle, around the oocyte, & as a stalk upon which the oocytes rest
- the oöcyte has reached its full size (0.2mm) & the follicle is ~10 mm in diameter
 
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What causes the development of the antrum?
- a release of hyaluronic acid from granulosa cells
- this is a very charged substance, so water will enter the follicle & fill the space
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Corona Radiata
granulosa cells that directly surround the ooctye & separate it from the antrum
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Cumulus Oophorus
- granulosa cells between the corona radiata & the circular follicle that surrounds the whole antrum
- looks like a pedestal on which the corona radiata & oocyte sit

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What does oocyte development require?
- high concentrations of estrogenthis comes from granulosa cells, which also release sex steroid binding globulin (androgen binding protein) to concentrate estrogen in the follicle
- estrogen levels can be >100X higher in the follicle than in the blood
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Can the Granulosa Cells produce estrogens directly?
- no, they do not have the capacity to do so
- Aromatase converts androgens secreted by Theca Interna cells to estrogens for faster oocyte growth
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How do nutrients get to the oocyte?
- because there are no blood vessels to the oocyte, nutrients must diffuse through the outer basal lamina through granulosa cells to the oocyte
- it's a long distance, but nutrient transfer is facilitated by:
- 1. gap junctions between granulosa cells & the oocyte
- 2. long cytoplasmic processes from the oocyte that invaginate & touch granulosa cells through the zona pellucida
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Theca Folliculi
- 2 layers of theca cells surrounding the granulosa cells (separated by the basal lamina)
- Interna: has abundant SER + lipid droplets (steroid producing cells making androgens)
- Externa: CT-like (become myofibroblasts)
- BOTH layers are vascularized

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Theca Interna Cells
- express receptors for LH
- when signaled they synthesize androstenedione & testosterone
- these androgens diffuse into the follicle's granulosa cells where FSH has stimulated the synthesis of aromatase
- (converts androgens → estradiol & estrone)
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What role do estrogens play outside of the ovary?
they stimulate endometrial gland proliferation (in the uterus) & mid-cycle, the LH surge
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Theca Externa
- cells will differentiate into myofibroblast-like cells that are LH responsive
- these contract during ovulation, which occurs in response to the LH surge
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Mature (Graäfian) Follicle
- follicle has reached its largest size (2.5 cm) & can be observed by ultrasound (during IVF)
- immediately before ovulation the antrum increases greatly in size
- even the corona radiata starts filling with fluid, which separates the oocyte + corona radiata in preparation for ovulation

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When does the oocyte progress from prophase of meiosis I to metaphase of meiosis II?
- "sometime between being a Secondary (Antral) Follicle & Mature (Graäfian) Follicle"
- an oocyte in a Mature Follicle is arrested in metaphase of meiosis II & will only complete meiosis if fertilized by a sperm
- all oocytes in any follicle prior to a mature one = primary (4n)
- an oocyte in a mature follicle = secondary (2n - haploid)
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Ovulation
- occurs shortly after a mid-menstrual cycle LH surge from the Anterior Pituitary
- causes contraction of theca externa myofibroblasts which expel the secondary oocyte, ZP, & intact corona radiata
- the released oocyte is captured by the oviduct (fallopian tube)
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What is thought to arise from constant rupture & repair of the mesothelium (visceral peritoneum)?
epithelial tumor development
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Corpus Luteum
- what's left of the follicle becomes a corpus luteum after ovulation
- the basement membrane (between granulosa cells & stroma) breaks down
- this allows an ingrowth of BVs
- there's a proliferation of both granulosa & theca interna cells
- it becomes a highly vascularized endocrine body whose granulosa cells produce Progesterone to support a possible fertilization event & pregnancy

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Corpus Luteum Cell Types
- both make Progesterone
- Granulosa Lutein Cells: paler, larger
- Theca Lutein Cells: are smaller & darker than granulosa LCs (& more tightly packed together); again make androgens (androstenedione) for conversion to estrogens

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How long will a Corpus Luteum persist during pregnancy & why?
- ~6 months, due to placental chorionic gonadotropin
- the continuous CL progesterone secretion maintains the uterine lining
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Corpus Albicans ('white body')
- all corpus luteum (from a menstrual cycle & pregnancy) will eventually degenerate & be replaced by a dense collagenous CT scar called corpus albicans
- after ~10 days of life for a corpus luteum, it begins to degenerate & progesterone levels fall with this degeneration
- the scar is larger for a corpus luteum of pregnancy than that of a corpus luteum of menstruation
 - contains few cells, appears 'cloud-like'
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Follicular Atresia
- death & resorption of the follicle
- can occur at any stage of folliculogenesis (primordial → mature)
- 98% of follicles (most) will become atretic
 - can see granulosa cells breaking up
- lots of cell death (apoptosis)
- remnant is the “glassy membrane (former basement membrane)
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Glassy Membrane
- a thick structure made of the basal lamina between the granulosa cells & theca cells that persists after follicular atresia
- some of the thecal cells from atretic follicles may remain & become interstitial cells that (along with the adrenal glands) become sources of sex hormones after menopause
  - a greatly thickening basal lamina from a former corpus luteum
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Uterine Tube (aka Fallopian Tube, Oviduct, Salpinx Uterina)
- consists of 4 segments -
- 1. Infundibulum: wide funnel-shape with fimbriae that have ciliated cells that create a 'current' to 'catch' an ovulated ovum
- 2. Ampulla: where fertilization usually occurs; longest part; has a highly infolded mucosa
- 3. Isthmus: short part
- 4. Intramural: shortest; is within the uterus wall
- salpinx = common name for tube in anatomy
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Uterine Tube Functions
- provides bi-directional transport:
- the ovum moves toward the uterus via ciliary action & peristalsis
- sperm move away from uterus (faster than swimming alone would allow)
- contains secretions that stimulate sperm maturation
- provides an environment for fertilization
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Ampulla
- the outermost part facing the peritoneal cavity is lined by a serosa (aka mesothelium, visceral peritoneum)
- then there's a muscularis, a 2-layer inner circular outer longitudinal muscle layer (expected in any organ that has peristalsis
- *most characteristic: highly infolded mucosa regions: longitudinal folds (resembling fern leaves)
- epithelium facing the lumen is made up of 2 types, simple columnar with & without cilia
- the non-ciliated cells are called Peg Cells; they are secretory

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Peg Cells
- secretory, so they don't have any cilia on their surface
- any place where you see a break in basal body staining must be where there's a secretory/Peg cell
- Peg cell secretions stimulate sperm capacitation
- this changes sperm movement & enables sperm to bind to the ZP & fertilize the egg

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Cyclical Changes that Take Place in the Ampulla
- estrogen being produced by growing follicular granulosa cells increases ciliogenesis
- progesterone produced from the Corpus Luteum increases the number of secretory cells
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