---start histo 11.27.96---

today we'll finish talking about the uterus, female repro tract and 
cycles. next week we'll go over the mammary gland and then because we 
have to touch base w/GI tract we'll finish up with that.

right now, we're going to see slides of the ovary:

in the ovary note the primary follicles high in the cortex and then note 
the multilaminar corpuscles....he points out a well devleoped follicle 
with cumulus whatever it was, corona radiata, theca interna and externa 
etc. another follicle, ready for extrusion, with ovum right next to edge 
of cortex. another atretic follicle shown. a collapsed, bloody, 
corrugated looking thing - an erupted follicle...also a corpus luteum 
with folded exterior part and some blood in center

another slide: shows mesothelial/peritoneal covering and tunica 
albuginea, and inside that the primary follicles. they lie in 
interstitium and don't respond to FSH yet. then they become multilaminar, 
egg gets bigger, have zona pellucida, call exener bodies, etc. these are 
secondary oocytes. ovum in center, thick zona pellucida (across which the 
microvilli from ovum and granulosa cells reach). then the granulosa, 
theca interna, theca externa. recall theca interna will become steroidal 
looking, and externa is fibroblastic. when follicle is becoming atretic 
you see the something becoming glassy, or hyaline in quality (either 
theca interna or externa)

he's not saying anythign NEW here. if he does, i'll write it down.

corona radiata looks more radial near ovulation.

when the follicle is shelled out you can see the vasculature in/beyond 
the theca externa - lots of blood around there.

follicle after eruption: theca interna and granulosa are luteinized and 
gettign corrugated. part of follicle near the surface of the ovary very 
very thin.

moving on to the uterus. it lies in phase with the ovarian cycle. there's 
the inner endometrium, the middle muscular layer - myometrium, and the 
outer perimetrium, which is CT with lymphatics, blood vessels, nerves, 
etc. 

the most interesting layer to dr weiss is th endometrium, because there 
the fertilized egg settles and implants during pregnancy.

consider an endometrium, under the control of estrogen. what is it like 
in the preovulatory phase?

two layers: the basalis and the functionalis. the pattern of structure in 
this endometrium is that you see a basement membrane of sorts with a 
surface cuboidal/columnar/or pseudostratified epithelium (dep on species 
et al.), then a glandular epithelium an some interstitial tissue between 
the glands. note: the surface epi is above the glands. the glands are on 
the basement membrane. at least according to what he drew on the board.

in the basalis you find straight glands lying on a poorly developed 
basement membrane on top of the muscularis. sometimes the glands actually 
reach into a pocket of hte muscularis. the basalis represents the part of 
the uterine gland NOT responsive to hormones or endometrial chnges during 
the cycle. it stays the same all the time, but is the basis for 
regeneration as well. rhesus work shows that when the endometrium was 
scraped away and removed so that you were down to the myometrium, 
following estrogen tx, the endometrium was fully regenerated. that's 
because of the basal glands in the myometrium. 

preovulatory/proestrus/estrus: estrogen dominates, endometrium is built 
up.
what happens is that under estrogen's influence - when FSH comes down and 
estrogen is produced, estrogen promotes growth of the epithelium and 
glands. the glands grow and this process starts early in the cycle and we 
have a tubular appearance to them in an endometrium under the influence 
of estrogen. 

there is also a rich blood supply. arteries penetrate muscularis, and are 
rather straight in the basalis, but spiral in the functionalis and are 
very adaptive and significant with some unique aspects. these arteries as 
they go up into the functionalis will break into capillary system, and 
then what happens esp in primates is that they form very thin walled 
spaces like lacunae, lake like spaces, quite dilated. are they 
capillaries or venules? whoknows. but they're thin walled and parallel to 
surface of endometrium. there are venous capillaries that drain them and 
become straight veins in the basalis like the arteries there. 



postovulatory/post estrus
approaching ovulation: endometrium becomes secretory. the glands become 
enlarged. the tissue becomes edematous. the glands start to sacculate 
within the functionalis (still straight in the basalis). glands secrete 
watery mucous very actively.


under progesterone in luteal part of cycle, the endometrium is getting 
VERY secretory. this is the endometrium that will receive the fertilized 
egg. the spiral arteries come up straight in basalis and spiraling up to 
functionalis. realize endometrium grows from 1-2 mm to 6-7 mm.

ovulation occurs at end of estrus phase. then uterus prepares to get egg.


so the endometrium is very sacculated and secretory
there are fibroblasts, lymphocytes, plasma cells within endometrium. some 
of the fibroblasts become rounded up with droplets int hem...these are 
characteristic of placental cells. they get some vacoules too. "decidual" 
cells. so changes in blood vessels, tissue, and glands.

if there is fertilization, extraembryonic membranes inc chorion will 
produce gonadotropins, signalling ovary to maintain the corpus luteum. by 
increasing amtss of estrogen and progesterone the corpus luteum will keep 
uterus very secretory and succulent. what happens if egg isn't fertilized 
and gonadotropin not produced you start to see degeneerative 
postovulatory changes in endometrium.

these changes vary. 

with primate/menstrual cycle, first the lacunae become full of blood and 
break down. blood is released from the lacunae and travels toward the 
veins no longer in vessels. it makes lakes and kind of dissects right 
into the tissue, causing chunks of the tissue to be "liberated" so the 
endometrium "bleeds off" if you will. 

god this sounds SO gross.

finally you're down to the basalis. as the corpus luteum fails and 
everything flakes off you have bloody fluid being discharged as the 
menstrual flow.

the basal parts of the glands like in the interstitial tissue with the 
bloody fluid above it. 

during the menstrual flow what happens is there is already regeneration. 
during end of flow epithelium grows from one gland to another, covering 
the underlying interstitum. and then you start another preovulatory cycle 
so the whole thing builds up again.

the functionalis is the part that grows under the influence of estrogen 
and progesterone. the basalis proper is NOT responsive to estrogen and 
progesterone, morphologically, but it does promote the growth of the 
functionalis in some way.

so. what happens in an ESTRUS cycle? in menstrual cycle the functionalis 
is sloughed off after the luteal/secretory phase of the cycle. this is 
after proestrus and estrus. in the latter phase of estrus, the animal 
ovulates, and endometrium becomes secretory as in menstrual cycle...THEN 
what? after estrus is metestrus and diestrus. in metestrus we begin to 
have the corpus luteum develop, and in diestrus the corpus luteum is in 
full flower. then, there's anestrus. in proestrus you recover from 
anestrus, start having estrogen. estrus: lots of estrogen, sexual 
receptivity, ovulation
metestrus: corpus luteum starts developing
diestrus: luteal phase.

if no fertilization you then get anestrus. what happens? when the 
hormones are withdrawn and you're in anestrus, the endometrium shrinks 
down into very simplified tissue, little more than basalis. but it 
doesn't slough off. since tissue is very edematous, it shrinks as 
hormones are withdrawn. macrophages act as bucket brigade, phagocytosing 
the interstitial tissue, then climb out of glands, and go out cervix, out 
of vagina. often in anestrus animals you see whitish trickle of d/c from 
vulva - these are the macrophages.

that's so weird.

additionally, and this isn't entirely understood, there is an immune 
response. tons of plasma cells come in. maybe some denaturation of tissue 
has occured. so there's an immune response which facilitates the action 
of mphages, causing lysis and phagocytosis. 

so the endometrium shrinks. not all the way to pure basalis, but a lot. 
and then its ready to grow under the influence of estrogen again.


preovulatory cycle rhesus: 2 wks
postovulatory cycle rhesus: 2 wks

proestrus and estrus each take 1-3 days.
anestrus endometrial reduction takes about 2 wks as well.


so reduction in menstrual uterus is much more dramatic.

understand that this is all under the control of the uterus. progesterone 
is secreted a bit before ovulation and then a lot more after ovulation. 

as estrogen amt increases during preovulatory phase, the high levels of 
estrogen turn off FSH which cause LH to be produced, which happens in a 
surge just before ovulation. after that progesterone amount increases 
dramatically.


one other thing. having a compulsion for completeness dr weiss is 
compelled to mention the last page of the male repro handout from the 
other day: the self test.

the cell on the left is a mucous producing cell. 2 is microvilli. 1 is a 
mucous droplet, 3 is a golgi, 

middle cell is engaged in steroid hormone production (smooth er!!) - thse 
are like cells of leydig, cells in adrenals, zona fasciculata of adrenal, 
part of ovary, etc. 1 is golgi, 2 is fat droplet, 3 is mitochondrion, 4 
also mitochondrian maybe dr weiss not sure,  5 smooth er, 6 small golgi, 
7 nucleus.

third : adrenal gland 1 zona glomerulosa 2 zona fasciculata 3 
reticularis. clear spaces bet cell columns are filled with sinusoidal 
venous vessels.

this pic represents an extraordinary evolutionary advance. it's really 
two glands. number 5 is the adrenal medulla ("chromaffin gland") and 
cortex is a separate gland . one gain from having them together is that 
the veins draining the cortex can supply the medulla and in so doing they 
bring the hormones (steroids)into the medulla, influencing the medullary 
secretions.


---end---