Lecture 16 - Manipulation of the Estrous Cycle

Question 1

Three ways we can manipulate the estrous cycle in the mare:

Answer 1

1. Alterartion of length of the luteal phase
   
   1. “Short-cycling” through induction of luteolysis
   2. Artificial lengthening through administration of exogenous progestins
2. Programming of the follicular wave
3. Advancing time of ovulation

Question 2

Can you start a new follicular wave by giving a horse a dose of GnRH, like you can in a cow?

Answer 2

No

Question 3

T/F: The dominant follicle in mid diestrus in the mare will result in ovulation most of the time.

Answer 3

False, it is very rare for the dominant follicle of the secondary wave in mid-diestrus to cause “secondary ovulation”. Most of hte time, it is anovulatory.

Question 4

When shortening luteal phase in mare, what is the dose of the prostaglandin Lutalyse (dinoprost) that we give?

Answer 4

5-10 mg IM

Question 5

Between prostaglandins Lutalyse (dinoprost) and Estrumate (cloprostenol), which one is closer to the native PGF2a? Which one is better to use due to less side effects?

Answer 5

Lutalyse is closer to the native PGF2a. Therefore, it is actually better to use Estrumate, becuase it is more targeted towards luteolysis, and has fewer systemic side effects.

Question 6

After administration of prostaglandin, majority of mares will be in estrus ____ days later.

Answer 6

3-5 days

Question 7

What are some of the symptoms mares have after administration of PGF2a?

Answer 7

Sweating, colic, “cow flop” feces - they have a rapid onset within minutes, and should reside within 45-60 minutes

Question 8

When giving PGF2a to shorten the length of her luteal period in the mare and induce estrus, there is an increased chance for her to have….

Answer 8

• Double ovulations
• Single ovulations with concurrent development of anovulatory hemorrhagic follicle

Question 9

In any given point in time with a group of 21 mares - one mare at each stage of her cycle - how many will respond to PgF and demonstrate behavioral estrus 3-7 days later?

Answer 9

12 (60%) - 10 will have a susceptible CL that will respond to the exogenous source of PgF, and two will be in proestrus period, where the CL has already weaned on its own.

Question 10

The interval to estrus in the mare depends upon _________ at time of PgF administration.

Answer 10

follicular wave status - mare with a larger follicle at the time of PgF administration will come into estrous and ovulate faster than the other mare who has a smaller follicle

Question 11

List three apparent failures to respond to administration of PgF in the mare:

Answer 11

1. Ovulation ocurred fewer than 5 days prior to administration, i.e., CL not susceptible to PgF
2. Mare with large diestrous follicle may ovulate rapidly without demonstrating overt estrus
3. Mare is not cycling, e.g., winter anestrus

Question 12

How can you avoid apparent failure to respond to PgF in the mare?

Answer 12

• Make sure it is the physiologic breeding season of hte mare
• Examine the mare by transrectal U/S PRIOR to PgF administration to confirm a CL and note the largest diameter follicle
• Plan accordingly - follicles grow 3-5 mm/day

Question 13

Luteal phase simulation with exogenous progesterone is appropriate for scheduled breeding within a window of approximately ____ week.

Answer 13

One

Question 14

Luteal phase simulation with exogenous progesterone is applicable even in the absence of a corpus luteum. Why?

Answer 14

• For vernal transition - prims the GnRH surge center when transitioning from winter estrus to her first ovulation
• Appropriate for select cases of abnormal cyclicity

Question 15

T/F: Luteal phase simulation with exogenous progesterone in the mare is efficacious even during the winter anestrus.

Answer 15

False

Question 16

Exogenous progestin administration inhibits _____, but it is unknown at exactly what level in the mare (negative feedback loop to hypothalamus and/or anterior pituitary).

Answer 16

Ovulation

Question 17

Describe the process of luteal phase simulation in the mare:

Answer 17

• Administration of exogenous progestin for 10-14 days (Regu-Mate - altrenogest).
• Abrupt withrdawal
• +/- PgF administration on final day (depends on season)
• +/- examination of follicular wave status - look at biggest follicle to know when to breed her
• Mare should be in estrus 3-5 days later, depending on the size of her follicle

Question 18

Does luteal phase simulation with progestin start a new follicular wave?

Answer 18

No, we are dealing with one already going on in the background.

Question 19

Mares in winter anestrus lack what three things?

Answer 19

1. Corpus luteum
2. LH stores - pituitary leaks LH all the time, so cannot store enough for LH surge
3. FSH-dependent follicular growth (only has small follicles that aren’t producing enough FSH)

Question 20

“Proactive” methods to quicken the onset of vernal transition include artifical lighting protocols by increasing the daylight length to 16 hours. When would you start this protocol and why?

Answer 20

Because we want the mare to transition by February 15th - we want to begin increasing her daylight length in the beginning of December to ensure that the mare will transition 2 months later. Progestin supplemenation towards the end of this period will help hasten time to first ovulation as well.

Question 21

Not being able to induce ovulation when mare has a CL using a GnRH analog is a big problem in horses. So how can we synchronize follicular waves between multiple mares?

Answer 21

Because we cannot start a new one, we need to dampen the one she already has and synchronize when they come into heat (estrus exppression) and when they ovulate. To do this, we can deprive the follicles of FSH by giving the mare estrogen and give her progesterone to prevent the mare from ovulating.

Question 22

Follicular wave manipulationg results in all mares having NO follicles > ____ mm in diameter at the time of luteolysis.

Answer 22

> 15-20 mm

Question 23

In mares, why can’t a single dose of GnRH analog during diestrus cause ovulation, like it can in the cow?

Answer 23

Because the LH-surge will be too brief, and mares have a long, drawn out LH surge before ovulation.

Question 24

Describe the role of estradiol in the P & E protocol of syncrhonization of estrus in the amre:

Answer 24

Estradiol inhibits FSH-dependent follicular growth via negative feedback of the anterior pituitary to inhibit FSH release. Discontinuationg then removes the negative feedback, allowing for FSH release, resulting in emergence of a new follicular wave.

Question 25

Describe the role of progesterone in the P & E protocol of syncrhonization of estrus in the mare:

Answer 25

• Simulates the luteal phase
• Suppresses estrus behavior
• Primes GnRH surge center if the mare is in vernal transition
• Inhibits ovulation in the absence of ongoing LH surge (i.e., mare in late estrus at start of protocol)

Question 26

Describe the role of PgF in the P & E protocol of syncrhonization of estrus in the mare:

Answer 26

Induces luteolysis, if mare still has a CL, to bring the mare into estrus.

Question 27

With the P and E protocol in mares, how long do we give her progesterone and estradiol for and when do we administer PgF?

Answer 27

P and E will be given for 10 days, and on the tenth day, we will give her PgF as well

Question 28

In the P & E protocol in the mare, time for initiation to breeding is _____ weeks.

Answer 28

3

Question 29

In the P and E protocol in the mare, when do we induce ovulation and breed?

Answer 29

Between days 18 and 19.

Question 30

Estrogen has a ___-feedback on the GnRH surge center and will upregulate ____ receptors on the surface of the dominant follicle.

Answer 30

positive, LH

Question 31

What are the requirements in the mare for effect administration of ovulation induction agents?

Answer 31

A follicle greater than or equal to 35 mm in diameter, and the presence of endometrial edema.

Question 32

What is the most commonly used ovulation induction agent in the mare?

Answer 32

hCG

Question 33

hCG has a long-acting ___-like activity

Answer 33

LH

Question 34

In response to hCG, over ___% of mares should ovulate in 24-48 hours

Answer 34

90%

Question 35

hCG is derived from a human protein, and therefore can cause _____ in the mare.

Answer 35

Anaphylaxis

Question 36

The difference in mechanism of action between hCG and deslorelin acetate (GnRH analog) in the horse is…

Answer 36

hCG directly binds to LH receptors on the dominant follicle, where Deslorelin acetate acts at the level of the pituitary, resluting in the release of endogenous LH.

Question 37

When using cooled transported semen programs, we most often administer the agent to induce ovulation when?

Answer 37

At the time of insemination

Question 38

One of biggest advantages of administration of agents that induce ovulation in advance of breeding with cooled transported semen is that it _____ the interval from insemination to ovulation.

Answer 38

Decreases

Question 39

When using frozen-thawed semen programs in the mare, it is important for the oocyte and hte sperm to meet in a “timely” manner, b/c frozen-thawed sperm only live for 6-12 hours, while oocytes live at most 12 hours. What are two protocols to ensure this happens?

Answer 39

1. “6 hourly protocol” - administration of ovulation induction agent –> examine mare every 6 hours –> inseminate upon confirmation of ovulation
2. “Timed protocol” - administration of ovulation induction agent –> scheduled inseminations (2 - once at 24 hours post ov. induction agent; and another time 40 hours post ov. induction agent)
3. Note - pregnancy rates are similar between the two

Question 40

The “timed protocol” assumes that gametes live for ___ hours.

Answer 40

8

Question 41

In swine, the CL is not susceptible to PgF until day ___ after ovulation due to low density of PgF receptors prior to that time.

Answer 41

12

Question 42

In order to induce estrus in pre-pubertal gilts, we can expose a boar to gilts of 150-170 days of age. However, it can require up to ___ days to induce pubertal estrus.

Answer 42

30

Question 43

We can transport gilts at about 160 days of age to improve response to boar exposure. The distance needs to be over ____ in order for it to work.

Answer 43

1 km

Question 44

T/F: Transportation of gilts at 160 days of age is enough to induce pubertal estrus.

Answer 44

False, it is not effective alone, however it improves response to boar exposure.

Question 45

Can we use GnRH, exogenous native FSH or LH to induce estrus in pre-pubertal gilts?

Answer 45

No, GnRH administration results in too transient a release of FSH and LH, and exogenous FSH and LH have too short of a half life

Question 46

What drug can we use to induce estrus in pre-pubertal gilts?

Answer 46

PG600: eCG + hCG

Question 47

When using PG600 to induce estrus in pre-pubertal gilts, they have a ____% pregnancy rate to times insemination.

Answer 47

60-70%

Question 48

When inducing estrus in pre-pubertal guilts, reproductive performance is improved if we….

Answer 48

wait to breed during subsequent estrus

Question 49

When shortening the luteal phase to induce estrus in cyclic gilts and sows, PgF will only lyse the CL on or past day 12. Timing to estrus can only be reduced by ______ days using administration of PgF on day 12.

Answer 49

3-4

Question 50

We can simulate the luteal phase in cycling gilts by giving them altrenogest for ___ days, and ___% of treated gilts will be in estrus __-___ days after withdrawal.

Answer 50

14 days; 85%; 4-9 days

Question 51

T/F: Simulating the luteal phase in cycling gilts using altrenogest increases farrowing rate over untreated cyclic gilts.

Answer 51

True

Question 52

Ovulation in sows does not typically occur during lactations of less than or equal to ___ days.

Answer 52

28

Question 53

If we wean sows between 16-22 days, sows will come into estrus ___-___ days later.

Answer 53

3-8

Question 54

At weaning in the sow, this removes inhibition of ___ and ___, leading ot follicular growth.

Answer 54

FSH and LH

Question 55

Weaning sows at 21 days yields highly predictable results. The estrus length is ___ hours and ovulation occurs ___ hours into estrus.

Answer 55

56; 41

Question 56

Several factors influence the length of post-weaning estrus, list three:

Answer 56

1. Parity: primiparous > multiparous
2. Short lactation length leads to longer estrus
3. Season - summer, fall is more problemmatic

Question 57

T/F: Boar exposure after weaning decreases time to return to estrus and ovulation.

Answer 57

True

Question 58

We can administer ____ at time of weaning in herds experiencing problems with failure of sows to come into estrus after removal of piglets.

Answer 58

PG600

Question 59

Administration of dinoprost (Lutalyse) to South American camelids has been associated with _______ and ____.

Answer 59

Idiosyncratic toxicity and death

Question 60

In south american camelids, luteolysis shoul dbe induced ONLY using _____.

Answer 60

Cloprestonel (estrumate)

Question 61

In the bitch, for successful estrus induction, ovulation and gestation of pregnancy to term, the inter-estrus interval must be at least ___ months. This is because the histologic repair of hte endometrium is not complete until ~ ____ days after the end of the most recent estrus, regardless of whether the bitch was pregnant or not.

Answer 61

5; 135 days

Question 62

How do dopamine agonists work in inducing estrus in the bitch?

Answer 62

Dopamine inhibits prolactin release; and prolactin may negatively affect GnRH secretion and/or ovarian responsiveness to FSH and LH

Question 63

Does estrogen work in inducing estrus in the bitch?

Answer 63

No, it only induces clinical signs of estrus, but ovulation may fail, and side affects may occur at high doses.