Histology, Block 4: Female Reproductive System

Front 1

what are the major divisions of the ovary? what's in each division?

Back 1

the cortex and medulla.

The cortex is full of primordial follcles.

the medulla is full of blood vessels, lymph, nerves, loose connective tissue.

Front 2

what hormones are made by the ovary?

Back 2

estrogen and progesterone are our steroid hormones.

also make peptide hormones - inhibin, activin, and relaxin.

Front 3

oocytes : how many are at birth, what stage are they in, and what happens to most of them?

Back 3

there are around a million at birth, all stuck in meiosis 1.

only 400 get used for monthly development. the rest are lost through atresia, often logarhythmically (fetuses might have 5 million, only a million at birth, 1000 left at menopause. only 400 used normally, rest are atresia, mediated by apoptosis of surrounding follicular cells).

Front 4

follicles - what divisions should we know?

Back 4

primordial, primary (with one or two layers of cuboidal follicular cells surrounding), secondary or antral (with an empty space in the

Front 5

What section(s) of the hypothalmus release GnRH?

Back 5

preoptic and arcuate nuclei

Front 6

describe the stages an oocyte goes through as it develops up through the primary stage.

Back 6

starts as a primordial follicle with squamous-looking follicular cells around it.

they begin to develop, become cuboidal (this is the primary oocyte). they proliferate, become multi-layered (and are now called Stratum Granulosum). The oocyte secretes the Zona Peludicda between it and the follicular cells (eosinophilic staining pink band gets thicker).

surrounding stromal cells make the Thecal Folliculi, a connective tissue mass around the follicle, which is divided into the:
theca interna: lots of LH receptors, in the presence of LH make lots of androgens (later converted to estrogen). lots of blood vessels too.

theca externa: full of smooth muscle and collagen.
Note - thecal cells are OUTSIDE the basal lamina of the follicular cells.

Front 7

secondary follicle? what's up?

Back 7

characterized by the fluid-filled antrum. after 6-12 layers thick, the granulosal cells move away from a point and a fluid filled cavity appears (liquor foliculi).

granulosa cells get pushed all the way to one side attached to the oocyte and is called the "cumulus oophorus." a small layer of granulosum cells are left surrounding the oocyte, these become the corona radiata. we're now at the mature follicle (graffian) stage.

note that the mature follicle is so thick that it extends through the entire cortex.

Front 8

how do the granulosa cells proliferate so much?

Back 8

the theca interna cranks out androgens in response to LH, some of which ends up in the granulosum. those cells have the ability to convert androgen to estrogen, and this drives their development.

Front 9

during oocyte development, what's the main target of FSH? what does inhibin target and where does it come from?

Back 9

FSH targets the granulosa cells. it makes them make aromatase (to make estrogen), it turns on FSH receptors.

FSH makes the granulosa cells make inhibin, which will tell the theca interna to crank out androgens...also drops FSH secretion

Front 10

what's the main target of LH?

Back 10

Lh's main target is the theca interna to induce the production of androgens.

NOTE: the LH surge before ovulation desensitizes the few LH receptors that exist on the granulosa cells, making it so you stop cranking out estrogen (estrogen begins to drop).

Front 11

what's up with ovulation? what's a polar body?

Back 11

it's the release of the oocyte from the graffian follicle. gets out of the gerinal epithelium (exits the ovary). note that just before this, it picked up and should have completed meiosis 1 (meiosis 2 doesn't happen until fertilization).

as this happens, one gets the lions share of the cytoplasm (both get equal DNA) and keeps going. the other is now the FIRST POLAR BODY.

Front 12

when does the second meiotic division happen?

Back 12

it begins immediately after the first happens, but arrests in metaphase.

doesn't finish until a sperm gets through - and produces the second polar body. so you can diagnose preggers with the finding of a second polar body.

Front 13

what's the corpus leuteum? what happens to it/in it?

Back 13

the former follicle's remnants.

changes shape, get lots of lymph/blood supply from the theca interna in what used to be the center.

Front 14

estrogen, progesterone, LH, FSH - describe the relative levels during the follicular phase

Back 14

After the previous cycle ends with crashing levels of estrogen and progesterone, GnRH/LH/FSH are un=inhibited and begin flowing.

LH causes release of testosterone from theca interna, FSH makes the granulosum cells turn it into estrogen. estrogen slowly rises in the follicular phase.

this extra estrogen keeps FSH and LH from getting too high and allowing another follicle to develop.

the extra LH/FSH makes the theca/granulosa cells more sensitive, so more estrogen gets made with non-increasing FSH/LH.

just before ovluation, estrogen gets high enough that it's a positive influencer of LH (especially) and FSH - this causes ovulation.

next, FSH crashes while LH goes down only a little, while the corpus luteum cranks out estrogen and progesterone getting the uterus ready.

immediately after ovulation, estrogen comes back down and slowly rises along with progesterone as the corpus luteum takes over.

progesterone slops to a stop, estrogen craters at the end, start all over.

Front 15

what generally stimulates the corpus luteum?

Back 15

LH - this is one of the reasons you know LH has to stay kinda high during the follicular phase, as the corpus luteum needs an inducer of some kind to crank out all that estrogen and progesterone.

Front 16

how is another follicle stopped from being produced during the luteal phase?

Back 16

all the extra progesterone affects GnRH - not just bringing down general levels, but also decreasing frequency of pulsations - so you DISCOURAGE FSH production and slightly favor LH secretion.

Front 17

if fertilization happens, what are the implications for the corpus luteum?

Back 17

becomes the corpus luteum of pregnancy instead that of menstruation.

the dropping LH/FSH levels from all that estrogen/progestone would normally kill off the corpus.

the BLASTOCYST release hCG (human chorionic gonadotropin) to keep the corpus luteum alive.

it is the main producer of estrogen/progesterone during the first trimester of pregnancy.

Front 18

when does the endometrium begin to proliferate and get ready for implantation?

Back 18

happens initially early in the cycle as the level of estrogen begins to go up, then goes up pretty steadily through ovulation and even more when all that progesterone gets made from the corpus luteum.

Front 19

how can you identify a follicle undergoing atresia?

Back 19

atresia can happen at any time.

if you see an oocyte in the middle of a follicle (not attached to one end) with granulosa cells moving into the antrum, it's probably atretic.

Front 20

does the estrogen peak happen before, during, after the LH surge? what happens to estrogen immediately after and why?

Back 20

estrogen peak preceeds the LH surge, as it causes the LH surge.

all that extra LH DE-sensitizes the LH receptors on the follicle, leading to DECREASED estrogen production immediately after the LH surge.

estrogen begins to creep back up due to secretion by the corpus luteum under the control of LH, which is still at pretty high levels during the luteal phase.

Front 21

what else keeps FSH down during the luteal phase?

Back 21

inhibin! it selectively suppresses FSH and is released by granulosa cells in response to FSH.

Front 22

we know the targets of LH and FSH in the early follicular phase (theca and granulosa, respectively). what happens in LATE follicular phase?

Back 22

FSH helps get the cells hyper-sensitized to LH...this helps them keep making estrogen despite feedback.

LH - this gets the granulosa cells ready to become "lutenized" - so after the LH surge when the granulosa cells they make progesterone. so, LH's target kinda shifts in late follicular phase to also include the granulosa cells.

Front 23

how is the dominant follicle selected?

Back 23

all about the level of FSH.

FSH levels in the early follicular phase are higher than in the luteal phase (due mostly to inhibition by progesterone). LH levels kinda stay up through the whole follicular phase, rise a lot during ovulation, then come back down HIGHER than before and slowly trail off.

Need that high FSH at the beginning of the cycle to determine the dominant follicle. FSH drops as the ESTROGEN comes up during the late follicular phase - this keeps more than one follicle from developing.

Front 24

so what does an estrogen antagonist do?

Back 24

this can cause multiple births - estrogen usually feeds back and drops FSH in the late follicular phase (before it becomes a POSITIVE regulator just before ovulation).

this dropping of FSH is required to keep multiple follicles from developing.

Front 25

pulsatile release of GnRH - what happens in premenopausal vs. post menopausal women in relation to relative LH/FSH? also, why is pulsatile GnRH important?

Back 25

Pulsatile GnRh is important because we know that if you have steady GnRH, you can't maintain LH/FSH (they both fall off completely). We know that lower GnRH pulses favor FSH, while more frequent GnRH pulses favors LH.

Premenopausal women have relatively LOW LH/FSH, with higher LH levels with continuous pulses...FSH is lower and doesn't saw-tooth much during a day.

POST-menopausal women have much higher LH and FSH (probably because lower hormone levels aren't feeding back to shut them down?)

they have high FSH levels than LH levels, and both are pretty saw-tooth

Front 26

oviduct - what does it look similar to? how can you tell the ampulla from the isthums?

Back 26

looks just like a seminal vessicle - 'cept the seminal vessicle is pseudostratified columnar while the oviduct is simple columnar.

the isthums is closer to the uterus ,and it's therefore a lot more muscular with only a tiny opening. the ampulla is white large with a lot of folds.

Front 27

oviduct epithelium - what it like? other cells around?

Back 27

simple columnar with cilia. also have a muscularis

also has peg cells

Front 28

what are the effects of estrogen/progesterone on the oviduct?

Back 28

estrogen causes increased force of ciliary beats, secretory activity, contraction of the muscularis, increases vascularity.

progesterone increases beat frequency

Front 29

sperm meeting egg - what interesting reactions happen?

Back 29

acrosome burrows hole in the zona pelucida.

CORTICAL REACTION - keeps only one sperm in, don't get more.

also get 2nd meiotic division to happen and get another polary body made.

Front 30

what are the layers of uterus, going from inside to out?

Back 30

endometrium, myometrium, perimetrium

the endometrium is the mucosa

the myometrium is the muscularis

the perimetrium is the serosa/adventitia

Front 31

describe the myometrium:

Back 31

biggest SM fibers in the body, and have 3 layers of muscle.

Front 32

estrogen, oxytocin, relaxin - what are the effects on the uterus?

Back 32

estrogen keeps tone and makes gap junctions.

oxytocin = uterus contraction

relaxin = inhibit contractions

Front 33

endometrium - describe its layers

Back 33

stratum basale = deepest, against the myometrium. it's always there.

stratum functunale = superficial, it goes up and down with the cycle

Front 34

what are the steps of the uterine cycle?

how do estrogen and progesterone affect it?

Back 34

start with the menstrual phase - rapid shedding of the stratum functunale, getting thinner.

then about 5/6 days in, begin the proliferative phase, lasts until ovulation - then get the secretory phase.

then premenstrual where it gets a little thinner (day 27/28), then menstrual phase.

estrogen causes the buildup, (estrogen levels mirror the thickness of the endometrium pretty closely).

progesterone is more about function - keeping it as a secretory organ

Front 35

what does the menstrual phase look like in the microscope?

Back 35

kinda torn up, ridgy, looks torn (the stratum functunale, that is)

Front 36

what does the proliferative stage look like?

what does the secretory phase look like?

Back 36

proliferative: see straight glands, no torn up funcunale


secretory phase:see big wide glands. thick.


PREMENSTRUAL identification isn't on the test.

Front 37

when does implantation happen? as in what days?

what makes hCG and what does it do?

Back 37

during the secretory phase, during days 21 through 24 (conception happened on day 1)

hCG comes from the implanted baby's synsychotrophoblast, and it rescues the corpus luteum and keeps it as an endocrine gland awhile longer (through the first trimester). it kicks out tons of estrogen and progesterone

note; hCG peaks at week 9 and then goes down.

Front 38

what's the decidual reaction? what cells are affected? what's the short term point? long term? hormones?

Back 38

if fertilization, the rising estrogen and progesterone levels encourage the STROMAL cells of the uterus to Hypertrophy and retain lots of glycogen/lipids

short term point is to provide more nutrition to the developing bady.

later, the growing stromal cells keep the baby from invading too far into the uterus.

also, the growing stromal cells become a kind of ENDOCRINE ORGAN, release relaxin (softens sevix), prolactin (stops immune response to fetus), prostiglandins

Front 39

what does a decidual cell look like?

Back 39

big and fat, kinda have skinny nuclei.

Front 40

talk about implantation (use words like trophoblast, cytotrophpblast, etc)

Back 40

cytotrophoblast (mitotically active) is the outer covering of the fertilized egg, which sends out little fingers (synsichotrophoblast) into the endometrium (epithelial lining).

synsichotrophoblast (not mitotically active) invades through epithelium into the stromal lining.

both of these make up the "trophpblast", which becomes the placenta?

essentially, the whole thing ends up in the wall of the uterus, with the synsychotrophoblast as the outer covering to the cytotrophoblast.

later on, the cytotrophoblast erupts out of the synsychotrophoblast. Buds of synsycho/cyto push out and are full of embryonic vasculature

Front 41

how does the placenta work?

Back 41

it exchanges gasses and stuff with the maternal blood, though the maternal blood shouldn't really enter the fetus.

get exchange across the cytotrophoblastic shell - those villuses formed from the inner synsychotrophoblast contain all the fetal blood vessels, they come up near the stromal blood vessels, gas exchange happens.

exchange happens in "intervillous space"

have anchoring villus and secondary villus

Front 42

so on a slide of a villus, what can we see?

Back 42

cytotrophoblasts are the light staining preipheral cells around the villus.

synchiotrohpoblasts are around the same place, but outside the cytotrophoblasts, but clumped, and very very dark.

the intravillous space is the empty space between vili where the mom's blood can float around and exchagne happens. exchange happens across the layers of cyto/syncho

Front 43

what's an anchoring villus?

Back 43

attached to the mom's side - the villus extended into mom

Front 44

what makes up the placental barrier?

Back 44

the cytotrophoblasts, the synsychotrophoblasts, connective tissue, and the fetal endothelial cells

Front 45

what are some important things that cross the barrier?

Back 45

gasses and nutrients (glucose).

steroid hormones.

transferrin

maternal antibodies cross (igG, giving immunity to newborn).

alcohol drugs viruses

Front 46

placenta releases hormones - what regulates this? what organ systems does it step in for?

Back 46

nothing! it's beyond regulation of either fetus or mom.

acts as gut, kidney, and lung for the fetus

Front 47

talk about the cyto/synchyotrophoblasts as an endocrine unit: what are the targets of the hormones produced?

Back 47

they become their own little hypothalmus/pituitary system.

cytotrophoblasts (inner layer) acts like the hypothalmus, while the synsychotrophoblasts (outer layer) act like the pituitary

the cytotrophoblast, like hypothalmus, makes GnRH, CRF, and TRF.

these act on the synsychotrophoblast to make hCG (acts like LH/FSH), TSH, ACTH, GH, and PROGESTERONE

targets are mom and baby

Front 48

what does progesterone from the placenta do? what other hormones are made by the placenta?

Back 48

after 1st trimester, corpus luteum shuts off and the placenta takes over.

the progesterone will inhibit mom's immune systen, make her breasts grow, and provides precursors to fetal adrenal glands. also stops contractions

inhibin A will stop FSH to keep more follicles from developing, hCS (to shunt food to baby)

Front 49

what happens to hCG as time goes on? what about prolactin? why isn't there milk production during pregnancy?

Back 49

corpus luteum dies, but the placenta keeps making it and levels stay high through pregnancy

prolactin gets higher through the whole pregnancy, a lot coming from mom. the high progesterone/estrogen levels keep its effects attenuated on milk - so wait 'till placenta falls out and then milk starts flowing

Front 50

what does the cervix look like under the scope? what transition is here?

Back 50

should be able to see glands.

has simple columnar epithelium.

have big cysts (mucous glands) out by themselves

pap smears pull off some of that epithelium.

note that as you go from cervix to vagina, now find stratified squamous epithelium

Front 51

estradiol, relaxin, progesterone - what are their effects on the cervix?

Back 51

estradiol makes watery mucous.

progesterone makes big thick mucous

relaxin - softens cervix, gets it ready for baby deliverin'

so - cervical mucuous is most abundant/watery during big release of estrogen JUST before ovulation, when you want sperm to come through

Front 52

what does the vagina look like under the scope?

Back 52

no glands, stratified squamous,

dual layered mucosa

it's really the only squamous epithelium we're going to encounter in the female

Front 53

what does estrogen do to the vagina?

Back 53

makes it store glycogen which flora turns into acid to kill the spermies

Front 54

breast tissue - what does the ductal tree look like? what happens during menstruation and pregnancy?

Back 54

changes throughout life, get more branches during puberty. little change during the menstrual cycle.

trees end in alveoli where milk can collect.

during pregnancy, the ducts and alveoli grow.

Front 55

lobes, lobules, etc - what's what?

Back 55

there are 15 to 20 lobes in a mammory gland.

one lactiferous duct connects to one lobe.

each lobe has lots of lobules attached to it.

note - each LOBULE is a functional unit.

glandular tissue present ONLY during lactation and pregnancy.

Front 56

what can you find around lobular ducts?

Back 56

lymphocytes coming in...also MYOEPITHELIAL cells and surrounding SM

Front 57

what cells make milk when pregnant?

when does proliferation and enlargening of the lobules happen?

Back 57

not the ductal cells - the alveolar cells make it.

proliferation is first half, lobule enlarging is second half

Front 58

what does pregnancy mamory gland look like?

Back 58

loose a lot of inter/intra lobular connective tissue (stroma goes down) to make room for ducts. still see flat myoepithelial cells, maybe some milk inside

Front 59

what about the lactating mammory gland?

Back 59

almost no connective tissue inside/outside the lobules.

all ducts are full of pink milk proteins

Front 60

what does the breast make?

Back 60

days 1-3 is colostrum, full of protein, vitamin A, IgA.

Then milk.

Front 61

estrogen, progesterone, and proalctin - what are their effects on the breast?

Back 61

estrogen: proliferation of DUCTS

progesterone: development of secretory (alveoli) units

think: ED, PA

prolactin: stimulates milk synthesis and release. normally kept off by dopamine when non-preggers.

goes up during pregnancy. it's blocked at the mammory gland by estrogen/progesterone, so it doesn't make milk until after those hormones disappear after the baby's born

Front 62

what does oxytocin do?

Back 62

it causes CONSTRICTION OF THE MYOEPITHELIAL cells to get milk around the ducts.

Front 63

what's milk let down?

Back 63

milk let down is the release of stored milk.

Front 64

what releases prolactin and oxytocin?

Back 64

prolactin and oxytocin are both released by suckilng.

prolactin makes milk, oxytocin helps get it into the ducts

Front 65

what happens to a woman's period during lactation?

Back 65

lots of prolactin inhibit GnRH, which can stop periods and you get amennorhia

Front 66

what's endometriosis?

Back 66

when endometrial tissue doesn't get into the vagina, it gets into the peritoneal cavity. it can implant there and still regulated by progesterone/estrogen, inflames and causes pain.

Front 67

why does estrogen drive cancer? how can you stop estrogen?

Back 67

estrogen is a mitogen that normally causes proliferation of the duct epithelia.

so, in cancer, target estrogen receptors or destroy receptors.

tamoxifen blocks estrogen receptors in the breast, but has opposite effect in uterus (causes it to develop) and causes bleeding/uterine cancer risk

use aromatase inhibitors to prevent making of estrogen

chemical castration - GnRH analogues which are given continually and prevent the release of LH and FSH.