Histo - Follicular Development Flashcards
Functions of the Ovary? (2)
gametogenesis (developing gametes formed here (oocytes))
Steroidogenesis –> Estrogens and progesterones
what do estrogens promote? Progesterone?
the growth of internal and external sex organs and female sex characteristics
Progesterone prepares internal sex organs for pregnancy
What’s in the medulla of the ovary?
in the medulla you have loose connective tissue, highly vascularized
you’ll have lymphatic vessels, nerves
What’s in the cortex of the ovary?
in the cortex you’ll find the follicles, which are embedded in richly cellular connective tissue.
what surrounds the cortex of the ovary?
right outside cortex is the tunica albuginia, which is a dense connective tissue
on the outside of the tunica albuginea is germinal epithelium covered with simple squamous to cuboidal mesothelium.
What are the phases to the ovarian cycle?
1) how long does it last
2) 3 phases?
28 days
Follicular phase (folliculogenesis)
Ovulatory Phase
Luteal Phase (formation of corpus luteum)
Follicular phase?
formation of the follicles.. you have a bunch of primordial follicles and then the selection of one mature follicle and that’s the one that will go through ovulation
1) When do the primordial follicles appear?
2) what part of the follicular phase is this?
3) histologically where are they?
4) what is the primordial follicles surrounded by?
5) what is inside it?
6) what is it arrested in?
5th month of development, early growth is independent of hormone stimulation.
first part!
in the stroma just deep to the tunica albuginea
surrounded by a single layer of squamous follicular cells
oocyte
prophase of the first meiotic division
Primary follicle is what?
what is the unilaminar primary follicle stage?
first stage of development of the growing follicle. the oocyte is starting to enlarge so the follicular cells that were originally flat start to become cuboidal.. and when they become cuboidal that’s a primary follicle.
the cells start to secrete proteins that resemble the zona pellucida that separates the oocyte and the follicular cells
Multilaminar primary follicle stage?
1) what is it called physiologically? histologically?
2) what happens to the follicular cells? What are they now called?
3) what else forms?
physiologically its called the secondary follicle, but histologically its still a primary follicle
here the follicular cells start to undergo stratification and form the stratum granulosum.. and the follicular cells are now known as granulosa cells
the zona pellucida and oocyte enlarges
you also have theca interna/externa develop which is right outside the basal lamina of the granulosa cells
Theca Interna:
1) where is it located
2) anything to note about vascularity
3) made up of what?
4) receptors?
5) what does it do?
inner layer and highly vascularized
made of cuboidal secretory cells
has a lot of LH receptors.
synthesize and secrete androgens that are precursors to estrogens.
contains fibroblasts, collagen bundles
What does the theca externa do?
nothing.. just an outer layer of connective tissue.
Secondary Follicle (Tertiary follicle physiologically?)
1) what is it characterized by? How does this happen?
2) what’s more prominent?
characterized by fluid filled antrum –> once the stratum granulosum reaches about 6-12 layers of thickness you get these cavities appearing, and eventually they’ll coalesce to form this antrum
increase in cell layers of zona granulosa
oocyte is larger
Theca Interna is much more prominent
What are some things you’ll see in the secondary follicle? (3)
Antrum
Corona Radiata
Call-Exner Bodies
Graafian follicle (mature follicle)
1) what stage of division has happened but what’s to note about this?
2) what’s different about the stratum granulosum here vs in the secondary follicle or even late primary follicle?
3) what is the thickened mound seen and what does it do?
4) what cells are anchored to the ovary?
5) what are the most internal granulosa cells called?
this is after the first meiotic division has completed but BEFORE ovulation
the antrum increases in size
stratum granulosum (that was getting bigger before) is now getting thinner –> preparing for ejection of the ovum
cumulus Oophorus –> thickened mound which is composed of gradually loosened granulosa cells in prep for ovulation
Corona Radiata –> layer of cells that are firmly anchored to the zona pellucida so they stay during ejection.. they aide in Fallopian tube uptake.`
Mural Granulosa cells –> line the wall of the follicle
thecal layer more prominent.
1) What does LH stimulate the theca interna to do? What can’t they do?
2) what do they do because of this?
3) how is this process initiated?
release androgens. but they lack aromatase so they can’t convert androgens to estrogen.
to do that they’re transported to the granulosa cells.. which DO have aromatase and that’s where they’re further processed.
FSH tells the granulosa cells to convert androgens to estrogens.
What happens to the primary follicles that are not chosen for development?
what mediates it?
most ovarian follicles are lost through follicular atresia, which is mediated by apoptosis of the granulosa cells.
Steps of Follicular Atresia? (7 steps)
1) cessation of what causes the start of it?
Steps:
1) apoptosis within the granulosa cells which is started by the cessation of mitosis.
2) granulosa layer infiltrated by neutrophils and macrophages which break down the zona pellucida.
****3) formation of the glassy membrane (basement membrane of the theca cells separate from follicular cells and increase in thickness, creating the wavy hyaline layer)*
4) invasion of granulosa layer by strands of vascularized CT
5) granulosa cells sloughing into the antrum
6) theca interna cells hypertrophy
7) Collapse of follicle as degeneration continues
8) Invasion of CT into the cavity of the follicle
What kind of oocyte is ejected during the follicular phase? what division does it go through?
what does it remain in until its fertilized?
As the primary oocyte is ejected, it finishes its first meiotic division becoming the secondary oocyte and remain in metaphase of the second meiotic division until its fertilized.
1) what is the ovulatory phase?
2) what is it triggered by?
3) what do you see histologically (what is it called) and how does it rupture?
hormone mediated process resulting in release of 2ndary oocyte from the Graafian follicle
triggered by LH surge
blood flow would stop in a small area of the ovarian surface overlying the bulging follicle –> follicular stigma –> elevates the oocyte then it ruptures
After ovulation, what happens to the theca interna in the follicle?
what is this called?
what happens to prevent more of this loss?
what does it become after the bleeding has stopped?
this is caused from bleeding from the capillaries in the theca interna that go into the lumen
the follicular wall collapses and the region can be filled with blood..
“Corpus Hemorrhagicum” (bleeding corpus luteum)
clotting and fibrosis occurs over the following weeks
Corpus Luteum
What happens during the luteal phase?
1) what is before the corpus luteum?
2) what does the follicular wall look like?
3) what cells go through what?
formation of the corpus luteum.
corpus hemorrhagicum heals, it’ll become the corpus luteum.
the follicular wall is thrown into these deep folds as the follicle collapses.
the cells of the granulosa layer and theca internal cells go through Luteinization
What is Luteinization?
1) what are mural granulosa cells changed to? What do they do?
2) what do theca interna cells become? what do they do?
breakdown of the basal lamina –> invasion of blood vessels –> cell transformation
Mural Granulosa cells are transformed to Granulosa Lutein Cells (80% of the corpus luteum)
synthesize estrogens, progesterone, and inhibin in response to LH and FSH
Theca interna celles –> become theca lutein cells (20% of corpus luteum)
secrete androgens that goes to granulosa cells and progesterone in response to LH DO NOT HAVE AROMATASE
what happens in the absence of fertilization to the corpus luteum?
1) how long does the corpus luteum stay
2) what happens to the cells?
3) what scarring will you see?
remains active for about 14 days, but degenerates 10-12 days after ovulation
the cells become loaded with lipids, decrease in size, and undergo autolysis
formation of a white scar (Corpus Albicans)
What happens if there is fertilization? what happens to the corpus luteum?
Starts to enlarge and produce progesterone and estrogen for pregnancy
Explain the relative levels of FSH, LH, Estrogen, Progesterone during the cycle
1) growing follicle, what happens
2) late follicular stage
3) ovulation
4) luteal phase
FSH is the principle hormone influencing follicle growth in the first 8-10 days.. it stimulates the granulosa and theca cells to secrete estrogen..
as estrogen increases, the FSH will be inhibited with negative feedback
in the late follicular phase Progesterone will kind of start to rise due to the increase in LH
LH surge triggers ovulation.
Luteal phase begins immediately after ovulation –> formation of corpus luteum –> which secretes a ton of progesterone and estrogen
when fertilization doesn’t happen, the progesterone and estrogen levels decrease.
Uterine Tube function (2)
4 segments?
what is the most common site of fertilization?
function is to transport the ovum from the ovary to the uterus.
also provide environment for fertilization and development of zygote.
divided into 4 segments –> infundibulum, ampulla, isthmus, uterine part
Ampulla
what are the three layers of the uterine tube?
1) outermost, what does it consist of?
2) middle, what 2 layers are seen and which one is thicker or thinner
3) inner layer, what does it contain?
Serosa –> outermost layer consisting of mesothelium and thin CT
Muscularis (smooth muscle) – > 2 parts, an outer longitudinal layer (thin), and an inner circular layer (thick)
Mucosa –> innermost, has lamina propria that are thin longitudinal folds projecting into the lumen. this is most numerous/complex in the ampulla
what is the mucosal lining composed of?
what 2 cell types are seen? important to know about ratio?
where is each most numerous? what do they do?
what is each stimulated by?
simple columnar epithelium
2 cell types! Ratio changes during hormonal cycle
1) ciliated cells –> most numerous in the infundibulum and the ampulla (help move oocyte along)–> stimulated by estrogen
2) PEG cells (non-ciliated) –> secretory cells that produce nutrient rich fluid to the ovum –> stimulated by progesterone
Uterine wall composed of 3 layers.. what are they?
1) what is the outer layer continuous with?
2) middle layer, what are the two layers and what’s one’s specific name?
3) what two layers are in the internal portion?
Perimetrium (outer serous layer) –> continuous with pelvic peritoneum
Myometrium (middle muscular layer) –> inner longitudinal and middle circular layer called “stratum vasculare” (where all your blood vessels are found)
Endometrium –> mucosa of the uterus –> has 2 layers.. stratum basalis and stratum functionalis
What’s the difference between the stratum basalis and the stratum functionalis
Basilis is the source of regeneration of the functionalis each month.
the functionalis is what is lost during menstruation.
functionalis has simple tubular endometrial glands and it has a simple columnar epithelial lining.
Blood supply to the uterus? (1 artery that does a bunch of stuff)
1) what’s the main artery?
2) what does it give off once it gets to the uterus?
3) branch from these?
4) what do these branch into and where are these found?
5) radial artery becomes what? and explain as it goes to the endometrium
Uterine A. –> come off the internal iliac artery, up to the uterus, gives off
1) 6-10 arcuate arteries which go through the myometrium
2) radial arteries from arcuate arteries.
3) radial arteries will continue up into the basal layer and give off some small straight arteries that stay there in the basal layer (not influenced by menstruation)
4) that radial artery then starts spiraling, called the “spiral artery”, part of which is in the basal layer, part in the functional layer
5) . goes up into the endometrium and form the capillary beds at the surface.
during menstruation in the uterus, which part of the radial artery will not change?
proximal part (straight arteries, part of the spiral artery)
distal part is going to be degenerated and regenerated with each cycle.
what are the three phases of the menstrual cycle?
Menstrual phase (days 1-5) –> correlates with follicular phase
Proliferative phase (5 - 14) –> correlates with follicular phase
Secretory phase –> 15-28 –> correlates with the luteal cycle
menstrual phase?
5 steps
step 5.. what remains?
how long does it last?
initiated by the regression of the corpus luteum because no fertilization happened
1) periodic contractions of the walls of the spiral arteries which cause the stratum functionale to become ischemic –> necrosis of endothelial cells –> Decrease oxygen to functional layer
2) trigger death and detachment of the endometrial glands
3) neutrophils and lymphocytes infiltrate the stroma
4) shed material (blood, uterine fluid, sloughing stroll and epithelial cells) constitute vaginal discharge
5) continuous until only the stratum basal remains
6) lasts 5 days
Early Proliferative phase and late proliferative phase?
1) what is the early proliferative and late proliferative phase located in?
2) what is it under the influence of?
3) what happens to the epithelium?
4) what about the arteries?
5) difference in endometrial glands in early and late?
in the FOLLICULAR PHASE
Early proliferative –> under the influence of estrogen.. stromal and epithelial cells are starting to proliferate rapidly because they’re trying to build up the functional layer
epithelium regenerates
secrete collagen and ground substance.
the spiral arteries lengthen but they’re only slightly coiled
endometrial glands start to reform, elongate in late phase
last about 9-10 days.
Secretory phase?
1) what is it associated with in the ovarian cycle?
2) what is it initiated by?
3) what happens to the functional layer and what hormone creates it?
4) what happens to the gland size, spiral arteries?
5) what’s the hallmark of the secretory phase??
LUTEAL PHASE
initiated by ovulation/production of progesterone by corpus luteum
progesterone causes the functional layer to thicken.
glands increase in size, more cells, more ground substance
spiral arteries have lengthened and become more coiled, extend nearly to the surface.
hallmark= endometrial glands are more tortuous and hypertrophied
lasts 13-14 days
Cervix
1) what’s to note about the endometrium here vs at the uterus?
2) what is absent here comparing to the uterus?
endometrium of the cervix differs from the endometrium of the uterus.
it has large branched glands, NO SPIRAL ARTERIES. it undergoes a little bit of change in thickness, but not as much as the endometrium
it undergoes changes in function related to transport of the sperm through the cervical canal.
parts of the cervix?
1) what projects into the vagina?
2) what part is considered the cervical canal?
3) what is the endocervic regulated by and what does it secrete?
4) junction?
Ectocervix –> projects into the vagina –> stratified squamous epithelium that’s continuous with vaginal epithelium
Endocervix –> simple columnar epithelium and considered the cervical canal –> secretes mucus –> regulated by estrogen (mid cycle, the amount of mucus increases 10 fold)
Squamocolumnar junction –> transition or transformation zone.
Nabothian Cysts?
blockage of the mucosal glands in the Endocervix
Squamocolumnar junction?
original?
new?
transition zone?
squamous epithelium of the ectocervix meets up with the simple columnar of the endocervix
you have an original SCJ and a new SCJ
The original –> neonatal squamous epithelium meets the endocervical columnar epithelium @ birth
New: result of dynamic remodeling during life of female –> Age, hormones, having children affects where the junction moves too
between old and new
What’s to note about precancerous lesions?
metaplastic changes can occur in this region, which constitutes the precancerous lesions that you hear about.. this is the location you’re hearing about (transition zone)
metaplastic change is having replacement of the simple columnar with stratified squamous. so it’s at the highest risk for neoplasia
HPV?
important to know, immature or mature?
what part does it affect?
most common sexually transmitted virus in the U.S.
infects the IMMATURE basal cells of the squamous epithelium (Ectocervix)
mature squamous cells that cover the ectocervix, vagina, and vulva cannot be affected
important types of HPV to know?
low risk types?
diagnosed by?
16 and 18
90% of HPV types cause genital warts, and those are low risk
Pap smear or biopsy
Vaginal wall consists of 3 layers, what are they?
1) are their glands? if so, where?
2) what is seen in the outer layer and what does it help with?
inner muscular layer –> stratified squamous epithelium.. has a lamina propria but no glands like the cervix and uterus
intermediate muscular layer (outer longitudinal layer that’s thicker, and inner circular layer(thinner))
Outer Adventitial layer –> inner dense connective tissue layer that has elastic fibers (giving the vagina strength), and an outer loose connective tissue layer
Epithelium of the vagina?
2) what causes epithelial cells to accumulate glycogen?
epithelium can undergo change
estrogen causes the epithelial cells to synthesize and accumulate glycogen as they migrate to the surface
the superior layer can be shed.
