WK 2 ( Oestrous cycles, mating behaviour and embryo signalling) Flashcards
(105 cards)
1
Q
Oestrous
A
Regular period of mating behaviour
2
Q
Dioestrus
A
The period between oestrous cycles
3
Q
Anoestrus
A
Absence of oestrous cycles
4
Q
Monoestrus
A
A single oestrous period per season
E.g. Bitch
5
Q
Polyestrus
A
Several oestrous periods per season
E.g. Mare + lots of other animals
Most domestic animals are seasonally polyestrus
6
Q
Induced ovulators
A
Continuous oestrous until mating
E.g. Rabbit, ferret
7
Q
Reasons for anoestrous
A
Pre puberty: Animal not yet cycling
Seasonal: Animal out of breeding season
Pregnancy: High P4 levels override cyclicity
Lactational: Sensory input suppress GnRH release
Stress: High cortisol levels suppress cyclicty
Pathology: Anatomical or physiological abnormality
8
Q
Follicular phase (time-frame)
A
From regression of CL to ovulation (~20% of cycle)
9
Q
Luteal phase (time-frame)
A
From ovulation to regression of CL (~80% of cycle) involves preparation for pregnancy
10
Q
Follicular phase
A
o PhasebetweenregressionofCLandovulationwhenfolliclesgrowandmature
Incorporatesprooestrus andoestrus
Dominatedbyoestrogen which:
- TriggersLHsurge
- Stimulatesoestrousbehaviour
- Preparesfemaletractforspermandovumtransportandfertilization
- Increases blood flow and secretions lubricates repro tract
- Causes myometrium contractions
Lengthoffollicularphasevariablewithinspecies
Thelongerthefollicularphase,themorevariabilitythereisbetween cyclesandindividuals makes AI harder
If fertilization occurs, the egg should reach the uterus around the beginning of Diestrus, when progesterone levels are at their highest
11
Q
Hormonal roles during the follicular phase
A
Early in the follicular phase (recruitment phase):
- Tonic center of hypothalamus produces fairly low levels of GnRH GnRH causes the anterior pituitary to release Gonadotropins (preferentially FSH at this stage of the cycle) stimulates follicular growth
- Oestrogen should be feeding-back to tonic entre at this stage (not surge center)
- Negative feedback loop keeps hormone levels relatively stable but other factors acting on the ovary still causes the follicles to grow
Medium follicle phase (selection phase):
- Towards the end of the proestrus stage, starts to move into selection phase
- As follicles grow oestrogen levels increase continue to feedback to tonic center causing release of GnRH shifts from preferential release of FSH to equal release of FSH and LH (due to medium sized follicles starting to produce another hormone called PGF which inhibits FSH production)
- Other factors on the ovary still allow follicles to keep growing in response to low level FSH
Large follicle phase (Dominance phase):
- Occurs during the Estrus phase
- Huge amounts of oestrogen being produced which feeds back to the surge center of the hypothalamus causing a surge release of GnRH = positive feedback
- Dominant follicle is releasing high levels of inhibin causing a shift to preferential release of LH causes breakdown of the follicle and ovulation
12
Q
The 2 cell, 2 gonadotropin model
A
Follicular steroidogenesis = production of oestrogen by follicles
Requires both the granulosa and the theca cells and both FSH and LH = The 2 cell, 2 gonadotropin model
Process:
- Theca interna cells have got receptors for LH LH binds to those receptors then through a cAMP – protein kinase pathway, it transforms cholesterol into testosterone
- The testosterone is then passed over to the granulosa cells (close relationship of theca and granulosa cells makes it an efficient transfer)
- Granulosa cells have receptors for FSH FSH binds to those receptors then through another cAMP – protein kinase pathway it transforms testosterone into Estradiol (potent form of oestrogen)
- Estradiol is then released by granulosa cells into circulatory blood travels to the brain where it has effects on behaviour and also travels to the reproductive tract where it causes increased blood flow and secretions and increased smooth muscle activity
- This is why both gonadotropins must be released throughout follicular phase to allow the production of oestrogen
13
Q
Follicular development
A
Follicular development occurs at random locations on the ovary (except in the mare)
As follicle grows it has more theca and granulosa cells able to produce more oestrogen so by the time it reaches antral phase it is has lots of theca and granulosa cells and high levels of gonadotropins so it can produce high levels of oestrogen
Antral follicles are only present when the animal is in her estrus phase
True corpus luteum only present during luteal phase – otherwise female would have high levels of progesterone all the time
By the time a follicle becomes dominant it is usually pushed to the edge to allow it access to the outside of the ovary for ovulation
The mare has ovulation bursa and only ever ovulate on one specific site of the ovary
14
Q
Follicular waves
A
Even during the luteal phase, recruitment, selection and early dominant phases occurring on the ovary but instead becoming fully dominant and ovulation occurring, these cells are becoming atretic and being resorbed
High levels of progesterone are suppressing follicular growth so that instead of becoming dominant they become atretic and are resorbed
After Luetolysis, another follicular wave will occur and this time the follicles will be allowed to become fully dominant and ovulation will occur as progesterone levels are low
Different species will go through different numbers of follicular waves (some species don’t have follicular waves but most domestic species do)
15
Q
Follicular dominance in regards to superovulation
A
Superovulation is more effective if the female is in the luteal or early follicular phase
Presence of dominant follicle can override the effect of FSH
16
Q
Effect of GnRH agonist on FSH induced superovulation
A
GnRH agonist minimises the amount of GnRH being produced –> suppresses follicle development
Two weeks pre-treatment with GnRH agonist suppresses follicle development so that no dominant follicle emerges
Subsequent FSH administrations is more effective
A larger follicle pool is recruited
17
Q
Characteristics of oestrus (high levels of oestrogen)
A
Anatomical/histological changes:
- Reddened vulva
- Open cervix (allows sperm entry)
- Cornification of vaginal epithelium (Theory - layer of dead cells protect vagina during copulation = less damage to healthy vaginal tissue)
Mucous changes:
- Cervical mucus thins and pH falls
- Vaginal lubrication
- Sperm transport
Fertility:
- Ovulation normally associated with oestrus – usually during but occasionally after
- Mating Behaviour
18
Q
Mating behaviour in mice & rats:
A
Pre-copulatory:
- Genital sniffing
- Display of “ear quiver response”
Copulatory:
- Assumes lordosis position
Post-copulatory:
- Genital licking
19
Q
Mating behaviour in cats:
A
Pre-copulatory:
- Calling
- Restlessness
- Poor appetite
- Head rubbing
- Frequent urination
Copulatory:
- Assumes lordosis position
Post-copulatory:
- Genital licking
20
Q
Mating behaviour in rabbits:
A
Don’t have oestrous cycles- they have ovarian cycles - are induced ovulators
Pre-copulatory:
- Mate seeking
- Permits make to sniff genitals
Copulatory:
- Assumes lordosis position
Post copulatory:
- Male falls off
- Male may thump
21
Q
Mating behaviour in dogs:
A
Pre-copulatory:
- Genital sniffing
- Tail deviation
Copulatory:
- Accepts male
Post copulatory:
- Genital lock
- Genital licking
22
Q
Mating behaviour in sheep:
A
Subtle signs
Pre-copulatory:
- Mate seeking
- May tail wag
- More frequent urination
Copulatory:
- Accepts male
Post-copulatory:
- Minimal
23
Q
Mating behaviour in cows:
A
Pre-copulatory:
- Genital sniffing
- Bellowing
- Mounting (males of females)
Copulatory:
- Accepts male
Post-copulatory:
- Minimal
24
Q
Mating behaviour in Pigs:
A
Pre-copulatory:
- Grunting
- Poor appetite
- Restlessness
- Nose-nose contact with mate
Copulatory:
- Assumes standing position
Post copulatory:
- Minimal
25
Pre-ovulatory LH surge
Dominant follicles are producing high levels of oestrogen
Circulatory oestrogen level reaches threshold level
Switch to positive feedback
Triggers surge center of hypothalamus
Surge of GnRH is released
Surge of gonadotropins are released – preferentially LH because of the amount of inhibin being produced by the dominant follicle
Preovulatory LH surge triggers ovulation (through a cascade of events)
26
Ovulation
Preovulatory LH surge triggers:
- Increase in blood flow to ovary and dominant follicle – this is also triggered by the hormone Prostaglandin E2 (PGE2) --> Edema
PGE2 is released from the ovary and increases blood flow to dominant follicle and ovary by increasing diameter of capillaries --> Edema
Increase in the production of the hormone (PGF2alpha) which increases the contraction of ovarian smooth muscle – putting pressure on the follicle wall & causes the release of lysosomal enzymes which weakens the follicle wall.
Shift from oestrogen to progesterone as follicular cells begin to transform into luteal cells which causes an increase in progesterone concentration, leading to an increase in Collagenase which breaks down the wall of the follicle
This cascade of events works together to weaken the follicular wall and cause ovulation
Act of ovulation/ Preovulatory LH surge also causes a wave of oocyte maturation which is important before fertilization can occur:
- Removal of meiotic inhibition (un-pause)
- First polar body is released haploid oocyte
- Fertilization
27
Luteal phase
Stage between ovulation (formation of CL) and regression of CL i.e. when the corpus lueteum is present
Incorporates metoestrus and dioestrus
CL secretes P4 which:
- Is essential for maintenance of pregnancy
- Exerts negative feedback on pituitary to restrict gonadotropin secretion
- Length of luteal phase consistent within species
- At end of luteal phase, corpus luteum regresses and P4 levels fall, leading to new follicular phase
28
Formation of a corpus luteum
Preovulatory follicle - granulosa and theca interna cells merge as follicle starts to break down
Corpus haemorrhagicum - small blood vessels rupture. Follicle implodes and folds inwards on itself
Functional corpus luteum - Large luteal cells were originally granulosa and small Luteal cells were theca
Occurs after LH surge – breakdown of follicular basement membrane
Theca and granulosa cells transform into luteal cells
Progesterone production follows the same pathway as oestrogen production
29
Progesterone produced by the CL
Progesterone produced by the CL has negative feedback to pituitary and hypothalamus - GnRH, FSH and LH are suppressed - little oestrogen is produced -ovaries will stay relatively quiescent
Progesterone has positive feedback effect on mammary glands and uterus preparing for lactation and implantation of the fetus (only has a few days to prepare the uterus before attachment)
Under the influence of P4 the uterine glands secrete materials into the uterine lumen. Progesterone inhibits the myometrium and reduces its contractility
30
Luteolysis
Brings about the demise of corpus luteum
If fertilsation doesn’t occur:
In a monoestrous animal corpus luteum will remain for a period until the next season
In a polyestrous animal corpus luteum will regress so she has another opportunity to mate
The corpus luteum has a natural life longer than the normal length of the luteal phase and production of luteolysin terminates it
31
The uterus and lueteolysis
Signaling pathway between Corpus Luteum and the uterus
Urartian vein comes out of uterus and winds around ovarian artery = close relationship with blood
When you have a fully intact uterus or contralateral uterectomy release of luteolysin from the that side of the uterus going to the ovary behaves just like normal (close relationship with blood)
When you have a ipsilateral uterectomy, the uterine veins have been removed which is the source of luteolysin the close relationship with blood is lost and the breakdown of corpus luteum relies on luteolytic activity coming out of the other side and then spreading through the circulation around the whole body until eventually getting to this side this is why there is a delay in CL breakdown
32
Signalling for luteolysis
The CL produces P4, which primes the uterus to produce PGF2alpha
PGF2alpha stimulates formation of oxytocin receptors (OtR) on the uterine endometrium
OtR respond to pulses of ovarian Ot, causing the release of more PGF2alpha
Positive feedback loop:
More PGF2alpha causes the formation of more OtRs - which causes more PGF2alpha to be released - huge surge in PGF2alpha --> signals breakdown of CL
33
Why PGF2alpha acts locally?
PGF2alpha leaves the uterus via the uterine veins which then drains into the ovarian arteries
PGF2alpha in ovarian vein destroys CL
34
Embryonic signalling
The embryo signals its presence via release of an antiluteolysin (in in a species dependent way)
May cause inhibition or diversion of PGF2:
- Oestradiol sulphate (in pigs)
- Prolactin (in rodents)
Embryo signaling MUST occur in time to prevent luteolysis
The embryo MUST be in place (and release sufficient antiluteolyic factor) at the right time and must be healthy enough to release signal
The embryo takes a few days to reach the uterus during which time the Corpus Luteum has produced P4 to prepare the uterus for pregnancy
Too early and the uterus is not ready and implantation cannot occur
Too late and the uterus is ‘past its prime; and implantation cannot occur
This is why donors and recipients must be synchronous to within 1 day (embryo transfer)
35
Embryo signalling - ruminants
Blastocyst is producing interferon tal (IFN-T) and it is interacting with the receptors on the endometrium of the uterus blocking oxytocin receptors positive feedback loop is blocked so PGF2 levels remain low and cant signal breakdown of Coprus Luteum
36
Embryo signalling - sows
Blastocyst is producing estradiol sulphate which changes the flow of PGF2alpha and instead of being directed to the veins it is being directed to the lumen of the uterus.
So it doesn’t get to the ovaries in a high enough concentration to cause breakdown of CL
One embryo is not sufficient to make this change happen (cant produce enough estrodiol) need at least 4 embryos to produce enough estrodial to change PGF2 flow to go into the lumen
Important that embryos are spread out so that the flow of PGF2is diverted along the whole length of the uterine horns
37
Embryo signalling - mares
Don’t know what the signal is that causes this change may have something to do with a particular protein (not enough evidence yet)
Blastocyst in mares moves around a lot before it implants thought that it does that to spread the message around the uterus to stop breakdown of corpus luteum (to make up for the fact that they only have 1 embryo)
38
Embryo transfer in sheep (timing of transfer)
Embryo removal before D13 leads to CL regression and return to oestrus at the normal time (because embryo hasn’t been able to signal that it is there)
Transfer of a D13 embryo to a D13 non‐pregnant ewe sees the CL persist
Transfer of a D13 embryo to a >D13 non pregnant ewe sees CL lysis (signal hasn’t happened in time)
39
Oestrous cycle in the mare
Seasonal polyestrous (long-day)
Oestrous cycle is ~21 days
FSH action early in diestrus may produce a mid-cycle follicle that will sometimes ovulate, but more usually regresses
Unique increase in FSH early in luteal phase (instead of the beginning of the follicular phase), this is because horses need a boost of progesterone at the beginning of the pregnancy so surge in FSH is due to the horses body assuming she is going to get pregnant and is preparing for pregnancy
Surge of FSH causes growth of follicles – these follicles usually don’t ovulate but do lutealyse which gives the mare a boost of progesterone at the beginning of pregnancy
40
Oestrous cycle in the bitch
Cycle stretched out over weeks
Luteal phase is stretched out a lot monoestrous animal only goes through one oestrous cycle a year
Pseudo-pregnancy – allows corpus luteum to maintain for the same amount of time regardless of whether she is pregnant or not don’t need to worry about embryo signaling
Lactation may occur regardless of whether pregnant or not
41
Pseudo-pregnancy in dog
False pregnancy, or pseudopregnancy, is a term used to denote a common condition in a non-pregnant female dog that is showing symptoms of pregnancy, lactation, or nursing, without producing puppies. The affected female dog shows these symptoms about a month or two after her estrus (heat) is over.
42
Oestrous cycle in the queen
Induced ovulatory hormone cycle is different
Non-mated queen will go through regular phases of oestrous but instead of the luteal phase they go through postoestrus (No CL formation) follicles grow but wont ovulate unless induced
If ovulation occurs progesterone levels are high and maintained until birth
Oestrous is suppressed during lactation after lactation oestrous cycles will begin again
Tom cat has spines on penis which stimulate cervix to induce ovulation however not very successful (50%) multiple mating attempts are often required (e.g. lions >100x per oestrous)
43
Ovarian cycle in the rabbit (doe)
Continuous follicular waves give constant high E2
Sterile mating induces ovulation - mechanical stimulus triggers LH surge
Pseudopregnancy lasts ~12 days (corpus luteum has a natural lifespan of ~12 days but if embryo signaling occurs it is maintained throughout pregnancy)
Pregnancy lasts ~31 days
44
Oestrous cycle in the mouse/rat (doe)
4 day waves of follicular growth and regression
Corpus luteum induced by mating
Pseudopregnancy last 12-13 days - return to oestrous
Luteolysin destroys CL in pseudopregnancy
If pregnant anti-leutolytic signal from embryo switches off luteolysin
Embryo signalling involves release of prolactin which block PGF2alpha
Pregnancy lasts 21-22 days
This system allows them to return to oestrous quickly and if they dont mate they don't have to waste time going through luteal phase
45
Oestrous cycle length in ewe
16-17 days
Follicular phase = 2 days
Luteal phase = 14-15 days
46
Oestrus length in ewe
24-28h
47
Time of ovulation in ewe
24h post onset of oestrous
48
Oestrous cycle length in cow
~21 days
Follicular phase = 2-3 days
Luteal phase = 18-19 days
49
Oestrus length in cow
12-18h
50
Time of ovulation in cow
20h post onset of oestrous
51
Oestrous cycle length in sow
~21 days
Follicular phase = 5-6 days
Luteal phase = 15-17 days
52
Oestrus length in sow
48-72h
53
Time of ovulation in sow
24-48h post onset
54
Oestrous cycle in mare
~21 days
Follicular phase = 5-16 days
Luteal phase = 15-16 days
55
Oestrus length in mare
4-7 days
56
Time of ovulation in mare
24-48 before end of oestrous
57
Oestrus length in bitch
9-10 days
58
Time of ovulation in the bitch
1-3 days post onset of oestrous
59
Oestrous cycle length in queen
14-21 days (unmated)
60
Oestrus length in queen
3-9 days
61
Time of ovulation in cat
25-50h post coitus
62
Oestrous cycle length in rat
4 days (unmated)
Follicular phase = 4 days
Luteal phase = o days (unmated)
63
Oestrus length in rabbit
Prolonged
64
Time of ovulation in rabbit
10-13 hours post coitus
65
Time of ovulation in rat
8-11 hours post onset of oestrous (nocturnal)
66
LH to ovulation interval in ewe
24 hours
67
LH to ovulation interval in cow
40 hours
68
LH to ovulation interval in sow
36-40 hours
69
LH to ovulation interval in mare
24-48 hours
70
LH to ovulation interval in bitch
24-72 hours
71
LH to ovulation interval in in queen
~ 24 hours
72
LH to ovulation interval in rat
~12 hours
73
LH to ovulation interval in rabbit
9-11 hours
74
Oestrous cycle in humans
Spontaneous ovulation and CL formation
Lifespan of CL determined by pregnancy
~ 28 day cycle
Follicular phase longer than in other
animals, equal length as luteal phase
LH surge is not at day 0 but day 14
75
Follicular phase Oestrous vs Menstrual cycle
Oestrous = 20% of cycle
Menstrual = 50% of cycle
76
Ovulation timing - oestrous vs menstrual cycle
Oestrous = start/end of cycle
Menstrual = middle of cycle
77
Luteal phase - oestrous vs menstrual cycle
Oestrous = 80% of cycle
Menstrual = 50% of cycle
78
Endometrial sloughing - oestrous vs menstrual cycle
Oestrous = No
Menstrual = Yes
79
Fertile period - oestrous vs menstrual cycle
Oestrous = 5% of cycle
Menstrual = 18% of cycle
80
Luteolysis - Oestrous vs menstrual cycle
Oestrous = Uterine PGF2alpha
Menstrual = Ovarian PGF2alpha
81
Menopause - Oestrous vs menstrual cycle
Oestrous = No
Menstrual = Yes
82
Proestrus
Early follicular phase
E2 rising
P4 falling
83
Oestrus
Late follicular phase
E2 highest
P4 lowest
84
Metoestrus
Early luteal phase
E2 falling
P4 rising
85
Dioestrus
Late luteal phase
E2 lowest
P4 highest
86
Embryo development (brief stage summary)
```
Zygote
2 cell
4 cell
8 cell
16-32 cell
Morula
Early Blastocyst
Blastocyst
Expanded Blastocyst (embryo signalling starts)
Hatched blastocyst (in mare this is the stage embryo would be moving around)
Elongated blastocyst (some species)
```
Each stage takes about 24 hours to develop
87
Breeding season for cattle
Spring/Summer
88
Breeding season for Dog
Late winter/spring
89
Breeding season for sheep/goats
Autumn
90
Breeding season for horse
Spring/ Summer
91
Gestation period for Dog
2-3 months
92
Gestation period for cattle
9 months
93
Gestation period for horse
11 months
94
Gestation period for sheep
~ 5 months
95
What happens to breeding season in the Tropics?
Constant day length
Either no seasonality and breeding all year
OR
One of the modifying factors becomes obligatory (usually nutrition due to monsoon)
96
Factors regulating breeding season:
1. Photoperiod (obligatory factor)
- Day length change
2. Temperature (modifying factor)
- usually no direct effects
- Indirect effects through nutrition
- Indirect effects through heat stress, e.g. Abnormal spermatogenesis (NT cattle) or libido
3. Nutrition (modifying factor)
- Effects of severe undernutrition (may delay seasons, result in silent oestrus, infertility etc.)
- High feeding levels ('flushing') may improve fertility but does not affect timing of breeding activity
4. Social stimuli (modifying factor)
- Male effect
- Progesterone priming (go through one silent oestrus at beginning of season)
97
Seasonality of breeding season - GnRH pulse generator
When hypothalamus is activated it releases GnRH in pulses - pulse pattern depends on affect on the pituitary
If you expose the pituitary to large quantities of GnRH continuously is stops working as the receptors become overworked - pulse release prevents this
Neural centers differentially sensitive to E2 feedback with season:
- Oestrous response to E2 changed with season in ewes (brain does not respond if animal is outside breeding season)
- LH secretion to E2 feedback changed with season (outside season high level oestrogen does NOT trigger LH pulse)
98
LH pulses (non breeding season vs breeding season)
Non-breeding season:
- Low base level, high amplitude, low frequency
Breeding season:
- High base level, low amplitude, high frequency
99
How is photoperiod transcribed?
Pineal gland
A neuroendocrine transducer
Produces melatonin at night day length changes affect melatonin production
Melatonin affects GnRH secretion and thus FSH and LH secretion
No direct effect in gonads
Has a positive or negative effect depending on species e.g. high melatonin levels stimulate GnRH production in short day breeders but inhibit it in long day breeders
Pinealectomy abolishes ability to register day length
In pinealectomised sheep breeding continues but at random regard to day length
Modifying factor e.g. nutrition or social factors may synchronize breeding season
100
Ram effect
Bring forward breeding season
LH surge in response to male
101
How can you manipulate the breedings season?
- Manipulation of day length
- Use of melatonin
- Use of gonadotropins
- Use of GnRH
- Use of social manipulation
102
Administration of melatonin
Manipulate the breeding season
- Implant in ear delivers melatonin for 6 weeks
- Advances breeding season when applied 8-12 weeks before normal start (in conjunction with ram effect)
- Only works in short day breeders
103
Administration of gonadotropins - manipulate breeding season
Use of PMSG and/or FSH in non-breeding season
| May need progesterone priming to cause oestrus & further cycling through CL maintenance
104
Administration of GnRH - manipulate breeding season
Repeat injections of GnRH to stimulate FSH/LH activity
GnRH agonists (long acting) decrease gonadotropin secretion in most species (down regulation of receptors - due to pulse production of GnRH)
Use of GnRH pulses are largely ineffective and impractical
105
Use of social factors to bring forward the breeding season in sheep
Use in advance to breeding season (2-3 months sheep)
Complete isolation of sexes 6 weeks beforehand
First 1-2 oestrous periods ‘silent’ and some short cycles
Hence first oestrous occurs 22-23 days or 26-27 days after introduction of ram
Use progesterone injection to ‘prime’ female – avoids short cycle
Prolonged progesterone (intravaginal pessary) stimulates oestrous behaviour at first ovulation
