8,9: Physiology of the Estrous Cycle - Volkmann Flashcards
basis of FM repro system / cycles is?
follicular waves
goal of FM repro sys?
to produce an oocyte that can be fertilized at predictable time (or multiple in litter bearing species)
what happens to majority of follicles that the ovary produces?
they become atretic
few will ovulate
at what stage are oocytes arrested in ovary?
diplotene stage of meiosis 1
what holds the oocytes in arrest?
meiosis inhibiting factor/AMH
what produces meiosis inhibiting factor/AMH?
granulosa cells
describe primordial follicles?
resting oocyte that contains oocyte surrounded by a layer of granulosa cells
T/F - the source of follicles throughout the life of a FM is infinite
FALSE - finite
why does only 1 follicle develop at 1 time?
b/c the follicle past primordial stage has layer of granulosa cells that sec AMH, suppressing the development of others
diff btwn structure of primordial and primary follicles
primary have 2 layers of granulosa cells
secondary follicle?
several layers of granulosa cells and zona pellucida around oocyte
what distinguishes tertiary follicle from secondary?
has antrum
structure of tertiary follicle?
lined inside by granulosa cells anchored to basement membrane
what 2 layers of cells are loc either side of the basement membrane of tertiary follicle?
granulosa cells anchored to BM in follicle
theca cell populations loc on other side of BM
what are the 2 populations of theca cells? fxns?
theca interna cells - endocrine organs
theca externa cells - skeleton that surrounds follicle => fibrous tissue
what triggers initial development of follicular waves?
gonadatropins
FSH - basal levels
what triggers antral formation?
conversion from secondary to tertiary follicles
higher FSH levels
what triggers the rise in FSH levels that triggers antral formation?
GnRH dependent from hypo
what receptors are on granulosa cells?
FSH
what receptors are on thecal cells?
LH
as granulosa cells dev, what hormone do they produce?
e2
what changes does e2 cause on receptors of granulosa cells?
induces formation of more FSH receptors
cycle continues - b/c follicles are stimulated to make more e2, which makes more FSH receptors on granulosa cells so follicles can develop and make more e2…
where does antral fluid come from?
fluid is secreted by granulosa cells
T/F - once a follicle develops, it can arrest again later
FALSE - once it begins, it cannot stop
in species except for the dog, what stage oocyte is ovulated?
secondary oocyte
what stage oocyte is released in the dog?
primary oocyte - meiosis must finish before fertilization can occur
fxn of LH?
to promote the follicle to mature and drive rupture of follicle at ovulation
matures graffian follicle to ovulatory follicle - causes ovulation
after ovulation, what role does LH have?
governs conversion of e2 producing follicle to a p4 producing CL
besides e2, what hormone do granulosa cells produce?
inhibin
what does inhibin inhibit?
suppresses FSH release
w/o FSH, no follicle or gonadal fxn can occur
when inhibin levels are high and FSH levels are low, where do granulosa cells get support from?
LH -> which drives follicle to next stage of a CL
what do theca cells take in and what do they use it to produce?
take cholesterol from circulation and convert it to progestogen -> utilize LH to convert it to testosterone
after theca cells make testosterone, where does it go and what happens there?
testosterone goes from theca cells, across BM, into granulosa cells, where it is converted to estrogen
via aromatase enzyme
what happens to granulosa cells after ovulation and why can it happen so quickly?
converted to CL b/c they are poorly vascularized and are loosely attached
what is level and fxn of FSH after ovulation?
high b/c inhibin is gone
it promotes the follicular wave to develop
what is considered day 0 of cycle?
when FM ovulates and a new follicular wave starts
why does a new follicular wave start when the FM ovulates?
b/c the dominant follicle produced inhibin - it is gone now so no inhibin and other follicles can develop in new wave
what hormone spikes after ovulation and drives development of new folliclular wave?
FSH
what changes does LH surge cause at ovulation and what hormone is secreted as a result?
follicle becomes CL
CL produces p4
what are e2 levels just after ovulation?
low [b/c now a CL, no longer a graffian follicle]
as one dominant follicle emerges during the follicular wave, what hormonal changes does this trigger?
dom follicle produces inhibin
FSH sec decrease as result
also e2 being produced, positive feedback to surge center
with dec FSH levels, how does dom follicle survive?
granulosa cells of follicle now rely on LH - look for ovulatory surge of LH to ovulate
if LH is not there [due to high p4] then the follicle does not survive and become atretic
what hormone suppresses the ovulatory surge of GnRH and subsequent LH?
p4 - works at level of hypo
T/F - p4 suppresses release of LH at level of pit?
FALSE
it suppresses GnRH surge at level of hypo - NOT LH surge from pit
so: you can give a FM a dose of LH and she will ovulate, despite high p4 levels - b/c LH is not inhibited - GnRH is inhibited at hypo
as a follicle becomes atretic, what happens to the hormone profile it produces?
e2 and inhibin levels fall
as inhibin levels fall, what hormone is allowed to inc?
FSH
which stimulates another follicular wave to occur
what does p4 do to the surge center?
it primes it - it inhibits the release of GnRH but induces expression of e2 receptors - so when there are enough e2 receptors present, the GnRH surge can occur -> ovulation will result
how does e2 promote ovulation indirectly?
sec from dom follicle
positive feedback to GnRH surge center -> eventually causes GnRH surge -> LH surge follows -> ovulation success
at what stages of FM life is it hard to produce GnRH surge to initiate cycling?
- pre puberty
- post partum [every time]
- post anovulatroy season [if seasonal animal]
clinically Tx FM to prime surge center by giving exogenous p4 using what products in what species?
regumate in mare
CIDR in cow
matrix in sow
T/F - e2, produced by large dom follicle, suppresses FSH secretion from pit gland.
False -> e2 does NOT suppress FSH sec
this was prior beliefs
now known: INHIBIN talks to ant pit to suppress FSH sec
t/f: in order to survive, all antral follicles require either FSH or LH or both
true
all viable follicles require gonadotropin support via FSH and /or LH
in spontaneously cycling animals, how can you start a new follicular wave?
by ending another one / the current one
make her ovulate the current follicle
why does ending one wave allow a new one to start?
b/c it gets rid of inhibin -> thus releasing suppression of FSH and allowing next wave to emerge in ovary
it is not uncommon for cows to have 2 or 3 follicular waves in one cycle. why is this NOT common in horses? horses tend to have only 1 follicular wave per cycle - why?
b/c mare has a drawn out LH surge (vs sharp LH surge of cow)
why is the prolonged LH surge of mare necessary?
b/c she ovulates 6-7 days after - so she is dependent on LH for follicle to survive
how do you shut off follicular development in mare?
e2 - shuts down ovaries - switch off follicular development
NOT inhibin - e2!
why does e2 shut down mare follicular development?
b/c e2 inhibits FSH secretion
immediately after ovulation, what structure is on the ovary?
corpus hemorrhagicum
why does corpus hemorrhagicum structure form?
collapse of follicle wall
disruption of BM (basement mem)
ingrowth of blood vessels
hemorrhage
after corpus hemorrhagicum develops, what cellular transformation occurs and what hormone does it secrete?
thecal cells [and maybe granulosa cells become luteal cells
luteal cells secrete p4
purpose of p4?
maintain pregnancy
therefore if not preg - get rid of p4 [source = CL]
what compound is converted into p4 by luteal cells?
cholesterol
what is present in antral fluid that helps with appropriate clotting?
anti coagulant
so: if hemorrhage occurs before ovulation, blood will not clot
and if she ovulates and releases follicular fluid, hemorrhage is followed by clotting -> corpus hemorrhagicum
developing CL occurs in what stages of estrous?
met estrus [occurring after estrus]
time btwn ovulation and mature CL
what process yields solidification of CL?
hyperplasia of thecal cells and stromal tissue
what is significant about met estrus stage CL?
insensitive to effects of PG
considered autonomous organ that cannot be destroyed
what is significance / importance of having CL refractory to PG?
if pregnancy is established, CL must be refractory, to ensure pregnancy is maintained
during met estrus, where is an embryo located?
in uterine tubes
in uterus by the time CL gains sensitivity to PGs [diestrus/anestrus]
mature CL is what stage of estrous?
diestrus
di estrus is what period of estrous cycle?
end of one heat to beginning of next heat [receptive
period]
so technicallly, met estrus and pro estrus are all a part of di estrus, b/c she is not receptive during these times
if not preg, what happens to CL?
lysed
what hormone lyses CL?
PgF2a (PG for short)
what domestic species does not have luteolytic mechanism
dog
where is PG F2a usually released from?
endometrium
what is general function of prostoglandin molecules?
inflammatory mediators
how does PG reach ovary from uterus in ruminants? in swine?
direct transfer of PG from uterine V into ovarian A - counter current exchange system for both
Ru: unilateral arrangement: PG from left uterine horn to left ovary and PG from R uterine horn to R ovary
swine: 2 uterine Vv are connected / anastomose so PG from either side can reach either ovary
how does PG reach ovary in horses?
no counter current exchange mech - therefore PG must go through systemic circulation and metabolism in lungs
therefore horse is exceptionally sensitive to PG - a small amt reaches ovary and is required to lyse CL
how does dog sensitivity to PG compare to horse and cow sensitivity?
dog extremely refractory CL so high dose needed to lyse CL - so high that side effects / systemic effects are too negative to dog
AND a dog dose would KILL a horse and cow
length of cow estrous cycle
21 d
what kind of cycle in cow?
non seasonal
poly estrous [one cycle leads to next]
how long is estrus of cow?
12-18 hours
when does cow ovulate relative to estrus?
12 hr after end of estrus
on hormone profile, how can you find PG?
cow cycle
precedes fall in p4
b/c cause effect relationship
how to find inhibin on cow cycle hormone profile?
opposite FSH
describe mare estrous cycle?
estrus length?
ovulation timing?
seasonal (long day breeder)
polyestrous
estrus 3-8 days [long sexual receptivity]
ovulation on last or 2nd to last day of estrus
MC day of standing estrus in mare?
last 2 days of estrus
how long is LH surge in mare?
2-3 days
how long is LH surge in cow?
short
what action does hCG have?
LH like
what % of large breed horses have tendency to double ovulate?
25%
twins are bad in horses
what is and what is important about transitional estrus or spring heat in mare?
- intermittent estrus, irregular or continuous heat
- lasts 3 weeks (about 3 follicular waves)
- first few waves secrete too little e2 to trigger ovulatory surge of GnRH
- fxn is like ‘puberty’ - to prime surge center
how does surge center get ‘primed’?
p4 primes it by inc e2 receptors on surge center -> allows positive feedback of e2 on surge center to trigger GnRH surge and LH surge and ovulation
drug to manage transitional estrus in mare?
regumate
progestegin (p4 like compound)
what is foal heat?
onset 5-10 days post foaling in mare
ovulation by day 18 post partum
highly fertile estrus
what is typical timing of foal heat?
10 days post partum
why might we skip the foal heat and not breed a mare at this time?
b/c it is highly fertile - but the subsequent estrus is even more fertile
greater chance of getting pregnant at estrus after foal heat
better to do this if she foaled early in season (consider 11 month pregnancy)
when/why might it be important to breed FM in foal heat?
if she foals late in the season, shoot for foal heat breeding so next year, she will give birth earlier (consider 11 month pregnancy)
what kind of cycle does ewe have?
length? ovulation timing?
seasonal [fall]
polyestrous
17 days
ovulation at end of estrus
ewe gestation length
5 months
for ewe, first ovulation after puberty and first ovulation of the season is more or less fertile?
does are the same
LESS
first diestrus is usually shorter than it should be
- if bred during first estrus of season, the short luteal period may be so short that she comes back into heat before her pregnancy is recognized so she will lose the first pregnancy
doe estrous cycle?
length?
estrus?
ovulation timing?
seasonal [fall]
poly estrous
21 d cycle
estrus: 1 day
ovulation at end of estrus
sow estrous cycle?
length?
estrus?
ovulation timing?
non seasonal poly estrous cycle 21 d estrus 1-4 d (MC 2 d) ovulate 3/4 way through estrus (MC 36-44 hr after onset of estrus)
sow has lactational anestrus. when she cycle post partum?
3-7 days after weaning
estrous cycle of bitch?
monestrous
every 5-12 months
MC 6-7 mos
less than 5 mos and more than 1 year btwn cycles is abnormal
what does monestrus mean?
one cycle does NOT lead to the next
no KNOWN physiologic connection btwn end of 1 and beginning of another cycle
describe diestrus in most species and what about bitch diestrus is different:
other species: dominated by CL (luteal period) followed by anestrus; is the period btwn 2 estrus receptivities
bitch: inherently 2 diff phases
- luteal period dominated by p4 then p4 levels become basal and nothing happens
unique about bitch endocrine estrous profile?
NO abrupt decline of p4 at end of luteal period
NO luteolytic mechanism
NO significant role of PGF2a, as in other species
what is different in bitch CLs than in other species CLs?
- CL of bitch has poor developed PG receptors
- to destory CL in bitch, b/c inherently refractory to PG, need BIG GUNS to destroy them - very high doses
how long are bitch CLs considered autoonomous?
how does this compare with other species?
- bitch: 25-30 days
- other species: 5 days
what hormones does CL depend on in bitch after day 30?
prolactin and LH
due to refractory CL, how to manage bitch cycle?
- lots of PG -> but too many side effects
- wait a month after ovulation and do something to suppress prolactin or LH sec -> CL will wither away and cease to fxn
when is the end of the luteal period in bitch? [met estrus]
there is not clear end
b/c no luteolytic mechanism that is known
what / when trigger for onset of pro estrus in bitch?
not clear
when does the luteolytic event occur in bitch? what is the purpose?
65 days post estrus - small luteolytic event - small PG surge
to destroy CLs - which are more receptive to PG effects
lysis is important to allow bitch to whelp
when do you see inc in e2 levels in bitch? what is causing the inc?
- massive inc in e2 levels before estrus
- prod by growing follicles
duration of heat [estrus and pro estrus] in bitch?
16 days average
half pro estrus and half estrus
hormone profile of bitch during pro estrus and estrus?
pro estrus: e2 and ends in LH surge
estrus: rising p4 levels [before ovulation]
what hormone changes occur before, during and after estrus in bitch?
rising p4 before
LH surge
2 days later - ovulation
how long is LH surge in bitch?
12 hrs
on what day of the cycle does counting begin in bitch? and other species?
others: at ovulation
bitch: LH surge - b/c it is measurable and ovulation is not directly easily measurable
in bitch, what hormone is used to indicate LH surge is near?
p4
what hormone is most measurable in bitch to detect when ovulation will occur?
why?
p4 b/c it is harder to catch the LH surge b/c it is short lived
p4 inc 2 days before ovulation
when it bitch most fertile?
why?
2 days after ovulation
4 days after p4 inc
b/c ovulatory oocyte needs to complete meiosis 2 before being fertilizable - bitch ovulates 1* oocytes and they must become 2* oocytes
what is 2-2-2 rule? for what species does it apply?
p4 levels reach 2
ovulate 2 days later
fertile 2 days later
how long are 2* oocytes fertilizable in bitch?
4 days
T/F - the mathematical opportunity for cow is less than a bitch b/c she is in standing estrus for a longer duration for each cycle
false - mathematics works out so that amount of time in estrus is same annually across species - duration of estrus and frequency of estrus works out so fertile time is approximately equal over annual basis
queen type of cycle?
induced ovulator w 3 or more matings
seasonal polyestrous
what is duration of non pregnant luteal period in queen?
30-35 days
what stimulates queen to ovulate?
coitus stim GnRH surge - vaginal stimulation by spines on Tom penis
more stimulation means more GnRH and higher likelihood of ovulation
t/f: non preg queen has a luteolytic mechanism
false - no luteolytic mechanism known in queen
t/f: preg queen has non luteolytic mech?
false - preg queen has luteotrophic mech to extend life of CLs
how long do CLs live in not preg queen?
in preg queen?
30 days if not preg
duration of pregnancy if preg
why don’t queen or bitch need / have maternal recognition of pregnancy mechanism?
b/c one cycle is not immediately followed by another cycle
they are NOT programmed to start a new cycle by default
camelid estrous cycle?
ovulation timing?
luteal period if not preg?
seasonally poly estrous
non seasona lin USA
ovulate 24 h post breeding - induced ovulators
non preg luteal period is 11-12 days
what stimulates camelid ovulation?
compound of seminal plasma of M induces GnRH surge
can be injected sub q and also work
if hembra mates but is not preg, how long before she cycles again?
14 days
how long post mating before you can measure inc p4 levels in preg hembra?
14 days
what hormone is measured in hembra blood to confirm preg?
what does this hormone indicate?
p4
indicates that she is maintaining her CL - suggestive of pregnancy
puberty 1* determined by what?
body weight relative to adult body mass
2/3
what variables affect puberty onset?
- body weight relative to adult body mass
- 2* photoperiod
- reversal of e2 inhibition on pituitary LH sec
t/f: first estrus typically fertile and luteal phase long
exception to the rule?
false - first estrus usually silent (no ovulation)
AND luteal phase often short
exception? bitch
pre pubertal - e2 inhibitory or stimulatory to LH surge?
inhibitory
what is required to lift reverse inhibitory effects of e2 before puberty on GnRH surge center?
p4 priming
t/f - domestic animals often experience reproductive senescence later in life
false - mare might
humans and primates do
what species is seasonality most outspoken in?
mare
sheep
queen
what hormone regulates seasonality?
melatonin
what secretes melatonin?
pineal gland
melatonin is secreted in response to what stimulus?
darkness
how does melatonin regulate cyclicity?
- darkness stim sec
- inhibits GnRH pulse generator in mares
- stimulates GnRH pulse generator in ewes
t/f: manipulating daylight exposure can completely control estrous cyclicity in seasonal animals
false - photoperiod fine tunes cyclicity
even with day lenght appropriate to favor cyclicity in animals, she will still enter a period of anestrus at some point in the year - her body will randomly decide when
what species is lactational anestrus?
sows
a little bit in beef cows
how to get post partum sows to cycle?
wean them
effects of M pheromones on FM reproduction?
and FM hormones on M?
M pheromoneinduces estrus beh in sows
FM pheromones provoke sexual interest in M dog
“ram effect” - ram induces cyclicity in ewes and also seen with pre pubertal gilt exposure to boar
bruce effect of rats - M causes abortion in pregnant rats
effects of nutrition on cyclicity?
age and BCS at puberty
nutrition plane to begin cycling after birth again
flush feed ewes to gain seasonal advances on cycles
spring grazing lush pastures advances 1st ovulation in transition mare
