Repro Endocrinology SA Flashcards
What are the stages of oestrus cycle based on vaginal cytology?
- proestrus (oestrogen dominant)
- oestrus (oestrogen dominant)
- OVULATION*
- metoestrus (transitional)
- dioestrus (progesterone dominant)
How are the bitch and queen defined reproductively?
> bitch
- mono-oestrus, non-seasonal, polytocus, spontaneous ovulatory
queen
- seasonally polyoestrus, polytocous, induced ovulator
- only shows follicular cycles not luteal (as CL required for luteal)
When does the bitch ovulate? What stimulates the initiation of oestrus?
- spontaneously ovulates at end of variable follicular phase (4-28d)
- no one knows what stimulates bitch to return to oestrus after long anoestrus
What is LH and FSH production dependant upon and what do these act to produce?
> dependant on
- GnRH (hypothalamus)
- steroids from ovaries (E2 +-, P4 always -)
LH and FSH act to synthesise OESTRADIOL
How long are the proestrus, estrus, pregnancy/diestrus and anestrus stages in the bitch?
- Proestrus 9d
- Estrus 9d (long cf. other animals)
- ovulation->CL*
- Pregnancy/Diestrus 60d (equivalent length of time so no need for maternal recognition of pregnancy really)
- CL regresses*
- Anestrus >90d
- spontaneous return to proestrus - unknown reason!*
How does LH change throughout the follicular phase?
> mid/late anoestrus - low LH levels and pulsatility - 1 week before proestrus - freq LH pulses ^ -> every 60-90mins, levels also ^ > proestrus - LH levels v, pulses v > late proestrus - LH reach peak 8-15ng/ml -> oestrus -> ovulation
How does FSH chance throughout the follicular phase?
>mid/late anoestrus - high FSH levels -increase throughout anestrus > 1 weeks before proestrus - modest increases, not as much as LH > proestrus - FHS low > late proestrus - peak occours ONE DAY AFTER LH - modest increase in mean level
Why is the discrepancy between LH and FSH peak times odd?
Both driven by GnRH
Which hormone is always present in higher concentration, LH or FSH?
FSH
How do oestradiol levels change throughout the follicular phase?
> mid/late anoetrus - levels remain low > one week before pro-estrus - levels remain low > pro-estrus - increase 10 fold > late pro-estrus - peak reached 1-3d before LH surge > diestrus (luteal phase) - some secretion
How do progesterone levels change throughout the follicular phase?
> mid/late anoestrus - low > 1 week before pro-estrus - remain low > proestrus - increase slowly, small amount > late proestrus - small increase from time ofLH surge to time of ovulation > diestrus - peak values reached post ovulation
What may be a good measure of pending ovulation in the bitch?
progesterone (quick and accurate by ELISA, ovucheck (premate))
Towards the latter stages, which hormone do follicles become dependent solely upon?
LH
What else occours at the time granulosa cells acquire LH-Rs?
start producing progesterone
what behaviour effects does oestradiol have?
- makes femlaes receptive to male advances
When does the LH surge occour wrt. oestradiol levels?
Immediately after peak oestradiol levels
What 2 things are initiated by the decrease in E:P ratio?
- LH surge
- sex behaviour
When does ovulation occours wrt LH surge?
~2d after
How does the ovulation of the canid bitch differ to most other species?
Ooocytes ovulated are immature and must still undergo 1st meiotic division
What has been suggested as the signal for compelteion of the first meiotic division in the bitch? What is the signal in most animals?
Bitch: rising P4 levels during luteinisation
Others: LH surge
How does the difference between ovulation in the canid cf. other spp. affect anything?
- normally environment of the follicle where oocyte grows and matures is important
- in canid the oviduct environment is important as this is likely where the oocyte will mature and complete 1st meiosis
How does P4 exert effects on cells?
- steroid so intracellular (slow changes)
- also exerts rapid changes (eg. affecting oocyte to -> 1st division) so potentially cell membrane too?
How does the progesterone profile of the pregnant and non prergant bitch differ?
IT DOESNT!
- well it does a tiny bit, slightly higher for slightly longer in pregnant bitch
- but not useful diagnostically
What is the only source of progesterone in the pregnant bithc?
CL
- no placental P4
What regulates progesterone secretion during diestrus? After the LH surge?
- LH
- progesterone itself (autocrine/paracrine) affects CL lifespan negative feedback
- after LH surge PRL becomes an essential luteotroph and regulates from ~d25
What drugs can induce luteolysis in the bitch? What would this cause in the pregnant bitch?
- GnRH continuously
- GnRH antagonist
- PR antagonist (eg. mifepristone)
*inhibit luteal PGF2a secretion - Inhibit PGF-R (FP) * look these up - don’t understand?
> abortion
In which spp is PRL the principle luteotroph?
Rodents
Which spp produce placental P4?
Sheep and humans
Do PRL levels increase in the non-pregnant bitch?
Yes (but not as much as pregnant bitch)
How are PRL and relaxin levels linked?
Both increase dramatically ~d25 after LH surge (and ovulation)
- PRL remains high where relaxin drops off around d60
What receptors are expressed thorughout CL life?
- PRL and LH
- PGF2a (hence can cause abortion at any time, just no endogenous luteolysins present naturally)
What can induce luteolysis exogenously?
- PGF2a
- P4-R ant
- GnRH ant
- GnRH agonist continuously
- DA ag (at high levles, as will v PRL)
What is the only time an endogenous luteolysin is produced by the bitch?
feto-placental PGF2a release pre-partum to induce parturition
Which is the ONLY pregnancy specific hormone in the bitch? Where is this produced? How can it be tested?
Relaxin
- produced in the placenta only
- enzyme immunoasssay available
What pathogy may PRL cause?
Pseudopregnancy
What does relaxin cause in males?
Testicle descent
When are relaxin levels increased in the bitch?
~21-24d after LH surge
How long post-parturition can relaxin be detected?
Levels drop at parturition but can be detected for 30d during lactation
Where does Relaxin act?
- pituitary cells -> PRL -> P4
- Luteal cells -> P4
What are the 2 options for control of oestrus in the bitch?
- OVH
- Hormonal (steroids) control
Which hormones may be used exogenously to control oestrus in the bitch? Which are NOT useful?
> Progesterone not useful as poor bioavailablitly orally and short t1/2
- Synthetic progestagens effective
- 1st gen (eg. MAP) potentially induce GH secretion -> acromegaly, mammary tumour, DM
- Proligestone - strong anti-gonadotrophic, weak progestagen, antioestrogenic (controls vulval swelling and bleeding)
Testosterone
- active by mouth
- BUT affects subsequent frertility
- causes vulval and clitoral enlargement
When will a pseduo pregnancy be seen?
~45d (6weeks) after end of estrus
What hormonal changes are asscoated with psedopregnancy?
- Progesterone NORMAL
- Associated with rise in PRL
What potentiates the development of a pseudopregnancy?
Any event causing rapid fall in progesterone
- OVH
- lysis of CL
- termination of pregnancy
How can pseudopregnancy be ended?
- usually regresses spontaneously
Tx - synthetic progestagens suppress PRL release
- oestrogens and androgens combo (probable act = P4)
- DA-ags (eg. bromocriptine) - but some old ones can induce vomiting
How do oestradiol levels change during the follicular phase of the queen?
- relatively high but variable
What regulates LH release in the queen?
Copulation -> massive LH release from pituitary
usually multiple copulations needed to produce sufficient LH for ovulation
When do progesterone levels rise in the queen? When do they fall?
- stay at baseline until ovulation after the mating-induced LH surge
- peak after 30 days
- in NON-preg animal, levels decrease from this point
- in PREG, maintained for 25-28 d
- if ovulation occours, even if mating is not succesful (pseudopregnancy) the queen will not return to estrus until after the levles of progesterone have fallen to baseline
When are PRL levels elevated in the queen?
Last 20d of pregnancy and throughout lactation
NOT in pseudopregnancy
What is the normal interoestrus interval of the queen? Mated queen? Pregnant queen?
Unmated or unovulatory: 21d (no luteal phase)
Mated, ovulate, NOT pregnant: 50d (luteal phase ~45d)
Mated, pregnant: ~65d
What is the interestrus interval determined by?
When P4 levels fall
When may pseudopregnancy occour in the queen?
- any non-pregnant luteal phase
- after sterile mating or spontaneously
What are the clinical signs of pseudopregnancy in the queen?
- lack of estrus
- NO physical signs (mammary development, lactation, behavioural change)
What causes the CL to persist beyond the usual 45d in a pregnant queen?
PRL (extra 20d)
How may oestrus be controlled in the queen?
> OVH
Hormones
- hCG: induces ovulation, delays subsequent oestrus as cat enters pseudopregnant state
- androgens: anabolic steroids daily 30d pre suspected estrus ,but induces masculinisation
- progesterone: ORALLY administered only. High doses, short time
- prevention (given as soon as calling begins) prevents conception and calling
- posteponement (given in anoestrus) may be temporary or permenant if repeated
Which endocrinology is better understood - the tom or the dog?
Dog
What is the action of LH in the male?
Stimulates Leydig cells to produce testosterone
What is the biological activity of relaxin?
- produced by placenta
- activity unknown but useful Dx of pregnancy