Endocrine 8

Front 1

describe the transition from estrogen to progesterone synthesis

Back 1

when the LH surge arrives at the ovary, it will change its synthesis from E to P (happens quickly)

at first, both are made, but true "reorganization that favors P synthesis" by about 24 hours after onset of LH surge

Front 2

what are the effects of increased progesterone synthesis?

Back 2

progesterone has feedback control at the hypothalamus

endometrium

and necessary for ovulation and the formation of the CL

Front 3

what drives follicle rupture? what else may play a role

Back 3

increased expression of many proteases, leads to degradation of the follicle wall

carefully coordinated series of events

the increased hydrostatic pressure from swelling of the follicle (with plasma) following LH surge may work in concert with the proteases to cause follicle rupture (but not sufficient alone)

Front 4

what causes meiosis in the oocyte to resume?

Back 4

LH surge causes meiosis to resume from prophase I, complete meiosis I and arrest in metaphase II

Front 5

describe the periovulatory changes to the oocyte. when is it fertilizable?

Back 5

fertilizable once it reaches metaphase II

Front 6

what drives the re-initiation of meiosis in the oocyte?

Back 6

when LH arrives, the loss of cAMP (cAMP locks the cell) so now the lock is gone

1) through desensitization of mural g.c. layer

2) uncoupling of transmural processes from cumulus layer to oocyte

3) activation of PDE3 (phosphodiesterase) which turns cAMP into AMP

Front 7

what's the effect of the LH surge on the cumulus layer?

Back 7

causes cumulus expansion, mediated by EGF family members and proteases

Front 8

what are the functions of the cumulus expansion?

Back 8

cumulus expansion allows extrusion of the oocyte (loosens it from the wall of the follicle)

hyaluronic acid in the cumulus matrix maintains dispersion of cumulus cells and facilitates sperm capacitation; cells contain ++ survival factors for the egg and sperm chemotactic factors

Front 9

where are the 2 places in the adult human body where angiogenesis occurs?

Back 9

1) the formation of the corpus luteum

2) the restructuring of the endometrium following menstruation

Front 10

what's a potential target for contraception besides endocrine disruption?

Back 10

targeting angiogenic process in the developing corpus luteum

Front 11

what are the primary hormone products of the corpus luteum? what are their functions?

Back 11

1) estrogen: endometrial proliferation during 1st half of the cycle, differentiation if fertilization, gonadotropin feedback, and "local actions ??" (not certain)

2) progesterone: endometrium, and in the event of fertilization, maintains pregnancy and CL

Front 12

progesterone has important ____ functions; there is ____-____ feedback

Back 12

progesterone has important local functions; there is autocrine-paracrine feedback

Front 13

what hormone maintains the corpus luteum in women?

Back 13

LH

GnRH and hence LH supports mid-luteal progesterone production vs. GnRH cessation and hence stopping LH would shut down progesterone production and cause pre-mature menstruation

Front 14

what makes up the bulk of the CL? why so important?

Back 14

vascular cells makes up about half the mass, so important to get progesterone out and into circulation efficiently

(critical for maintaining pregnancy)

Front 15

the CL is a very complicated gland. what are the main 4 cell types?

Back 15

steroidogenic cells derived from g.c. and theca cells

number of immune cells increases

Front 16

what defines the end of the menstrual cycle?

Back 16

"death" of the corpus luteum during a non-fertile cycle, the process is called luteolysis

Front 17

what's our best guess for how luteolysis works in a human?

Back 17

loss of trophic support probably represents a decline in sensitivity to LH

(just a hypothesis, we don't really know)

Front 18

what's corpus luteum rescue?

Back 18

the process during a fertile cycle by which the early embryo secretes hCG (chorionic gonadotropin) that has a high affinity on LH and CG receptors to keep progesterone alive and thus maintain the CL for about 7 weeks until the placenta takes over progesterone production

Front 19

what hormone prevents contraction of the uterus?

Back 19

progesterone maintains quiescence of the myometrium of the uterus

important to maintain early preganancy; its declining levels causes cramps around the time of menstruation

Front 20

the CL differentiates from the ____, specifically the ____ and ____ cells

Back 20

the CL differentiates from the follicle, specifically the granulosa and theca cells

Front 21

the lifespan of the CL depends solely on the fate of the ____

Back 21

the lifespan of the CL depends solely on the fate of the oocyte

(2 weeks in non-fertile cycle vs. 7 weeks in fertile cycle)

Front 22

steroid and peptide products have ____ and ____ effects to regulate cycle length

Back 22

steroid and peptide products have local and central effects to regulate cycle length

Front 23

______ of the CL is essential for the next cycle of follicular growth vs. ____ of the CL is essential for pregnancy

Back 23

regression of the CL is essential for the next cycle of follicular growth (through loss of P relieving negative feedback on FSH) vs. rescue of the CL is essential for pregnancy

Front 24

what vasculature is lost with menstruation? then what happens?

Back 24

spiral arteries

then re-formed under the influence of estrogen in the first half of the cycle, the site of angiogenesis every cycle

*potential cycle target

Front 25

other than the spiral arteries, what other part of the endometrium is lost and re-formed every cycle?

Back 25

the straight necks of the glands

Front 26

what's causes the very dense layer at the apical surface of the endometrium and what do you call it?

Back 26

the zona compacta, forms under the influence of progesterone

Front 27

describe the changes of the glands and stroma caused before ovulation. caused by ____

Back 27

estrogen

Front 28

describe the changes of the glands and stroma caused after ovulation. caused by ____

Back 28

estrogen and progesterone

Front 29

what hormone is involved in "pre-decidualization"? and what is it?

Back 29

progesterone -->

pre-decidualization of the luminal epithelial cells causes increased gland production and changes in luminal morphology (cells become rounded and store glycogen)

Front 30

what's estrogen's primary role on the endometrium in the first half of the cycle? what are the intermediaries?

Back 30

stromal proliferation and

increases the expression of the progesterone receptor (PR); preparing the endometrium to respond once P is present

Front 31

what are 4 major effects of progesterone during the second phase of the cycle?

Back 31

Front 32

summarize what happens when progesterone levels decline

Back 32

P withdrawal via luteolysis --> protease release**

Front 33

what's behind the loss of blood during menstruation?

Back 33

as spiral arteries in the functionalis constrict, there is extravasation of blood into the stroma (the uterine lumen)

Front 34

what's the main theme of this lecture?

Back 34

that chemical messengers, in the form of steroids, especially estrogen and progesterone are integrating the female reproductive system in time and space

so that the hypothalamus, pituitary, ovaries, and uterus can all work in concert with one another

Front 35

where does fertilization occur?

Back 35

at the junction between the ampulla and the oviduct

Front 36

what is a fertilized egg called when it enters the uterus and implants?

Back 36

a blastocyst

Front 37

what stops most of the sperm from reaching the oocyte?

Back 37

the cervix, cervical mucus, only about 100k of 250 to 500 million reach the uterine cavity; fewer than 100 reach the distal end of the oviduct

Front 38

where do sperm mature?

Back 38

in the epididymis

Front 39

how long can the cervix store sperm?

Back 39

up to 72 hours

Front 40

_____ occurs during the passage of sperm through the cervical ____. what 3 things does this process involve?

Back 40

capacitation occurs during the passage of sperm through the cervical mucus

this imparts:

1) the ability to undergo the acrosomal rxn

2) hypermotility and

3) ability to bind to the zona pellucida

Front 41

what allows the sperm to get through the cumulus matrix?

Back 41

hyaluronidase activity expressed by the head of the sperm

Front 42

what are the 4 steps of fertilization starting with the sperm arriving at the zona pellucida?

Back 42

1) the sperm arrives at the zona pellucida, where

2) contact and binding initiates the acrosomal reaction i.e. the breakdown of the acrosome and the release of enzymes that

3) degrade the ZP and

4) an acrosome process that is an actin filament will form and make contact with the oocyte's plasma membrane

Front 43

what are the consequences of the actin filament of the sperm making contact with oocyte's plasma membrane

Back 43

this initiates a wave of calcium within the oocyte; this results in:

1) fusion of the sperm plasma membrane with that of the oocyte --> allows the release of nuclear, genetic material from the sperm into the egg

2)the second is the cortical reaction

Front 44

explain the initiation of the "cortical reaction"

Back 44

as part of the calcium wave initiated by the acrosomal reaction, there is the fusion and release of vesicles called cortical granules that line the oocyte and contain very important enzymes

this is called a block to polyspermy (i.e. fertilization by more than one sperm)

Front 45

how does the cortical reaction block polyspermy?

Back 45

the calcium wave initiates fusion of these cortical granules and release of their enzymes into the space between the egg and the ZP; they break down the ZP proteins into very specific fragments, which fuse together and form an impenetrable barrier to additional sperm; the primary block to polyspermy in humans (occurs within a couple of minutes)

Front 46

what 3 things happen as far as meiosis in response to the sperm binding?

Back 46

in response to sperm binding, there is

1) the completion of the second meiotic division and 2) the extrusion/formation of the second polar body, so 3) within 2-3 hours after the arrival of the sperm, you can see the male and female pronuclei (under light microscopy);

Front 47

describe the pronuclei and zygote in terms of haploid and diploid.

Back 47

each haploid genome in the pronucleus fuse together to form one complete diploid genome and within about 24 hours, there will be the first division

Front 48

what happens to the zygote before implantation?

Back 48

several rounds of cell division occur before implantation, while the zygote and ultimately the early embryo transits the oviduct and enters the lumen of the uterus

Front 49

what's a zygote?

Back 49

a zygote is a fertilized egg prior to first division (you can see the pronuclei)

Front 50

what is still intact at the 2-cell stage of the early embryo? why is it important?

Back 50

2-cell stage, ZP is still intact, very important because it prevents the early embryo from adhering to the wall/the endometrium and implanting

these cells divide again and again to form a morula (a solid mass of cells) and develops into a blastocyst (i.e. a morula that has developed a cavity

Front 51

what critical step allows the blastocyst to contact the cells of the endometrium and implant?

Back 51

the blastocyst hatches from the ZP, which is very very important because the cells of the blastocyst are then able to contact the cells of the endometrium directly

Front 52

describe the events right after fertilization:

where does fertilization occur? when does cell division occur? what are the next two phases?

Back 52

*fertilization occurs at the delay in the junction of the ampulla and the isthmus,

*cell division begins within a couple of days,

*by day 4-5 you have a blastocyst and

*by the end of day 7 or 8, you have adherence and implantation into the endometrium

Front 53

what essential hormone does the early embryo produce? why so important?

Back 53

even at these early stages of development, even especially (day 4, morula), cells of the early embryo begin to produce hCG and rescue the CL, so an early pregnancy test would show positive even if you haven't missed your period yet

Front 54

what is compaction?

Back 54

compaction: the physical constraint of the growth of the early embryo; the ZP constrains the volume in which the early embryo has to develop, so as these cells divide, they have increasingly smaller space in which to divide

Front 55

what does compaction cause?

Back 55

compaction forces polarization of these cells early on in division due to limited states, which results in division in a basal vs. apical manner, the differentiation of cells of the inner cell mass as they divide across this axis into the pluriblast and the trophoblast

Front 56

what does the pluriblast become? what does the trophoblast become?

Back 56

pluriblast becomes the embryo

trophoblast becomes the placenta and extraembryonic membranes

Front 57

simply put, what 2 steps follow sperm penetration of the ZP?

Back 57

sperm penetration of the ZP --> initiates acrosome reaction --> initates calcium wave

Front 58

what 2 things does the calcium wave allow?

Back 58

1) allows fusion of sperm and egg, and

2) the cortical reaction, a block to polypsermy by the "hardening of the ZP"

Front 59

when does cell division begin?

Back 59

cell division begins within about a day after the pronuclei fuse

Front 60

describe the timeline of fertilization

Back 60