Reproduction - Comparative Oestrus Cycles & Pharma

Question 1

What is the total length of oestrus (ovulation to ovulation) for the mare?

Answer 1

21 days

Question 2

How long is oestrus in the mare (standing behaviour as Day 1)?

Answer 2

4-8 days

Question 3

What is the length of the oestrus cycle in the sow?

Answer 3

21 days

Question 4

What is the length of oestrus in the ewe?

Answer 4

17 days

Every 17 days in the fall & winter, te ewe will ovulate (if she isn’t impregnated right away).

Question 5

What is the length of oestrus in the bitch?

Answer 5

93 days.

Question 6

What is the length of oestrus in the queen?

Answer 6

It’s variable.

Question 7

What is the length of the oestrus cycle in the woman?

Answer 7

28 days.

However, women don’t mark their ovarian cycles by the start of oestrus, but by the appearance of menses, and thus they mark the menstrual cycle rather than the oestrus cycle. Ovulation occurs in the MIDDLE of the woman’s menstrual cycle, whereas ovulation typically occurs a few days after the start of the oestrus cycle in domestic animals.

Question 8

In domestic animals, is the follicular phase of the oestrus cycle longer or shorter than the luteal phase?

How does this compare with the two phases in the woman?

Answer 8

In domestic animals, the follicular phase is much shorter than the luteal phase.

In humans, the follicular & luteal phases are the same length (14 days & 14 days).

Question 9

How long does oestrus last during the oestrus cycle (ie., when the animal is receptive) in the mare?

Answer 9

4-8 days

Question 10

How long does oestrus last during the oestrus cycle (ie., when the animal is receptive) in the cow?

Answer 10

4-24 hours

(also cited as 12-36 hours)

In cow, oestrus tends to be nocturnal; oestrus must be observed, marked by standing when mounted, Flehmen, lordosis, swollen vulva, etc.

Question 11

How long does oestrus last during the oestrus cycle (ie., when the animal is receptive) in the ewe?

Answer 11

24-48 hours

The ram has to be fast!

Question 12

How long does oestrus last during the oestrus cycle (ie., when the animal is receptive) in the sow?

Answer 12

48-96 hours

(2-4 days)

Question 13

How long does oestrus last during the oestrus cycle (ie., when the animal is receptive) in the bitch?

Answer 13

7-13 days

Note that the bitch only ovulates one every 93 days, so if she doesn’t become pregnant during the 7-13 days she’s in heat, then she has a very long period – almost three months – before she will ovulate again. In reality, the bitch goes through a very long period of anoestrus when she won’t come into heat at all, so she might come into heat less than once a year.

Question 14

How long does oestrus (heat) last during the oestrus cycle in the queen?

Answer 14

4-10 days. This is when you hear queens yowling.

Question 15

How long does oestrus (heat) last in women?

Answer 15

There is no “oestrus period” in the same way domestic animals go into heat.

Question 16

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.

When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the mare, how long is this follicular stage?

Answer 16

Variable, but about 7 days.

Question 17

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.

When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the cow, how long is this follicular stage?

Answer 17

4 days

Question 18

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.
When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the ewe, how long is this follicular stage?

Answer 18

Three days

Question 19

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.
When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the sow, how long is this follicular stage?

Answer 19

Seven days

Question 20

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.
When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the bitch, how long is this follicular stage?

Answer 20

18 days

Question 21

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.
When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the queen, how long is this follicular stage?

Answer 21

Variable

NB the luteal phase is 40 days, and the entire oestrus cycle is variable, so it’s definitely less than 40 days! Probably a few days.

Question 22

The follicular phase of the oestrus cycle is when oestrogen is dominant; it is rising as the dominant follicles prepare to ovulate and the granulosa cells continue to convert testosterone from the theca cells, using aromatase, into oestrogen.
When the oestrogen plasma concentration reaches a threshold, oestrogen will switch from providing negative feedback to the hypothalamus for GnRH production and the anterior pituitary for LH secretion to positive feedback.

In the woman, how long is this follicular stage?

Answer 22

14 days. Same as the luteal phase.

Question 23

Physiological interventions can be used to achieve cyclical synchronisation in a herd or to induce ovulation (can be for an individual animal or in a herd). The ways these physiological interventions work are not all completely known, but in general, they stimulate or inhibit endogenous reproductive hormones via the hypothalamus-pituitary-gonadal axis.

Give an example of a physiological intervention used to achieve cyclical synchronisation in a herd of ewes.

State how it works, as well as the advantages & disadvantages.

Answer 23

**Ram effect. **

• remove rams from ewes during anoestrus up to six weeks before expected oestrus
• isolate rams for 3-4 weeks, then re-introduce to ewes
• majority ewes ovulate w/i 6 days
• priming & then removal of progesterone (sponges, IM
  injections) pre-intro ↑ ewes in oestrus - priming extends the luteal phase, then removing the sponge at the same time – sudden reduction in progesterone, like luteolysis – causes them to start ovulating together
• *Advantages**: cheap, can affect whole herd
• *Disadvantages**: only works @ certain times of year (ie., just before start of natural breeding season); doesn’t work in deep anoestrus (eg., July)

Question 24

What type of physiological intervention can be used to induce ovulation in ewes?

Answer 24

Ram effect. Same idea as in achieving synchronization in a herd.

Question 25

Physiological interventions can be used to achieve cyclical synchronisation in a herd or to induce ovulation (can be for an individual animal or in a herd). The ways these physiological interventions work are not all completely known, but in general, they stimulate or inhibit endogenous reproductive hormones via the hypothalamus-pituitary-gonadal axis. ## Footnote Give an example of a physiological intervention used to achieve **cyclical synchronisation** in a herd of **cows**. State how it works, as well as the advantages & disadvantages.

Answer 25

Can use a **teaser bull**, but oestrus (heat) is very short, ranging from 12-36 hours, and is highly variable among individual cows. Physiological intervention is not as successful in synchronising cows, as they are not seasonal breeders and thus their oestrus isn't as predictable or detectable. Their cycles are slightly longer than ewes at 21-24 days, and they typically display oestrus at night (so difficult to detect).

Question 26

What are pharmacological interventions that can be used to achieve synchronisation in a herd of ewes?

Answer 26

1. Progesterone (P4) - eg. sponge 2. Prostaglandin F2-alpha (PGF2a) - injection 3. Melatonin

Question 27

How is progesterone used to synchronize a herd of ewes? What are the advantages & disadvantages?

Answer 27

Basically: introduction of P4 via sponge extends/coincides with luteal period -- gets all the sheep on same luteal phase -- then sudden removal "tricks" them into thinking luteolysis has occurred as P4 levels suddenly drop off. Then, FSH & LH rises & follicular phase can begin. Specifically: - in cyclic ewes, P4 suppresses pre-ovulatory release of LH/FSH → inhibits follicular growth & ovulation - upon removal of progestagen, (-) feedback removed → gonadotrophins ↑ → E2↑→ oestrus → ovulation - in anoestrus ewes, P4 withdrawal is complemented by follicle-stimulating treatments eg. PMSG (pregnant mare’s serum gonadotrophin) - Sponges, implants via intravaginal, IM, SC; intravaginal sponges most common, provide good results after natural mating - sponges contain: synthetic progestagens, fluorogestone acetate (FGA) or medroxy progesterone acetate (MAP) **Advantages**: can even work in June, when ewes are in deep anoestrus **Disadvantages**: progestagen treatment must last for length of luteal phase, ie., 12-14 days, so sponge must stay in; labour-intensive

Question 28

How are prostaglandins used to synchronise a herd of ewes? What are the advantages and disadvantages?

Answer 28

**PGF2α & analogues** synchronize oestrus in *cyclic ewes*: - ***induce luteal regression*** → P4 ↓ → (-) feedback removed → LH/FSH ↑ → ↑ follicular growth → E2 ↑ → oestrus w/i 2-3 days → ovulation * *Disadvantages**: - CL only responsive between days 5-14 of cycle (otherwise refractory), so would need two injections 10-14 days apart - imprecise & labour intensive; not very successful, really - induced oestrus leads to poor fertility, poss. due to limited exposure of tract to P4 (progesterone prepares increases uterine milk & reduces uterine motility in preparation for implantation)

Question 29

How is melatonin used to synchronise oestrus in a herd of ewes? What are the advantages & disadvantages?

Answer 29

- ↑ darkness = ↑ melatonin secreted by *inhibited* pineal gland (ewes come into oestrus as days shorten; when pineal gland is inhibited due to less neural excitation from daylight, it secretes MORE melatonin) **An increase in melatonin stimulates GnRH from the hypothalamus, triggering LH & FSH production ie., oestrus cyclicity** - used to advance onset of oestrus in seasonally anoestrus ewes * *Disadvantages**: - treatment must be initiated after period of LONG day-length (ie., summer), then elevate melatonin for ~5 weeks; maybe easier to herd ewes in a barn & regulate lighting.

Question 30

What are non-physiological methods of inducing ovulation in ewes?

Answer 30

1. **Nutrition** - flushing with Lupin grains (might increase leptin in adipose tissue) 2. **Genetics** - "F" (fecund") gene, aka Boorola in Merino breed 3. **Gonadotrophins** 4**. Immunisation / Vaccines**

Question 31

How are gonadotrophins used to induce ovulation in ewes?

Answer 31

This refers specifically to **Pregnant Mare's Serum Gonadotropin (PMSG), aka Equine Chorionic Gonadotropin (eCG)** - In equids PMSG has only LH like activity, *but in other species **it has activity like both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).*** - commonly used in concert with progestogen to induce ovulation in livestock prior to artificial insemination. – administered during **follicular phase** in cyclic ewes or after **progesterone priming (insertion & removal of P4 sponge)** in anoestrus ewes Pregnant mares secrete the hormone from their endometrial cups between 40 and 130 days into their gestation, and once collected, it has been used to artificially induce estrus in female sheep, goats, cattle, and swine. Despite being less pure than pituitary extracts from sheep, goats or swine, PMSG tends to be used because of its *longer circulatory half-life*.

Question 32

How does immunisation help to induce ovulation in ewes?

Answer 32

- reduces inhibitory effects of **inhibin or gonadal steroids** on pituitary (FSH/LH) & hypothalamus (GnRH) - leads to more gonadotrophins → ovulation rate ↑

Question 33

In cows, what are the pharmacological interventions used to synchronise oestrus?

Answer 33

1. Progesterone (ie. priming with sponge) 2. Prostaglandins (PGF2a)

Question 34

How does progesterone (P4) synchronise oestrus in cows? What are the advantages & disadvantages?

Answer 34

- ***mimic luteal phase*** of cycle - usually combine with **luteolytic factor** to ensure CL has regressed by time of ***P4 withdrawal*** (eg., E2 at start of treatment is preferred over using prostaglandin at end) - Using **PMSG at P4 removal ↑ follicular maturation & ovulation** (PMSG has FSH & LH effects) **Advantages**: sensitizes HPG axis in non- cyclic cows ∴ works with inactive ovaries - oestrus & ovulation occur earlier & with more precise timing than following prostaglandin injection alone **Disadvantages:** must last for length of luteal phase, ie., 12-14 days, so sponge must stay in; labour-intensive 

Question 35

How are prostaglandins used to synchronise the oestrus cycles of cows? What are the advantages & disadvantages?

Answer 35

- **PGF2α *induces early luteal regression*** - from Day 6-16 of cycle, injection induces luteal regression - leads to start of new follicular phase → P4 ↓ → (-) feedback removed → LH/FSH ↑ → ↑ follicular growth → E2 ↑ → oestrus → ovulation **Disadvantages**: - For group of cyclic cows at different stages, PGF2a must be given in a *second injection* 11-13 days after first dose because the CL from days 0-5 is refractory; all cows will have functional CL by second injection - variable results in lactating dairy cows 

Question 36

Synchronisation of the oestrus cycle isn't as common with mares as it is with ewes, since horses are not typically raised as food livestock and thus ensuring they all produce offspring to meet the market at optimal prices is not required. However, controlling oestrus in individual mares is important for several reasons. What are three reasons?

Answer 36

1. **Birthdate**: Race horses are all "born" on Jan. 1. This is important as the performance of two-year-old horses in qualifying contests are watched carefully. It is therefore important that foals be born as close to Jan. 1 as possible. (NB gestation length is 330 days or ~ 11 months, so mare must get pregnant by early March for Jan. 1 foal) 2. **Live cover**: Better for planning with studs. 3. **Embryo transfer**: Need to synchronise donor & recipient

Question 37

What are the main ways a mare's oestrus cycle can be manipulated when she is in the ***transition phase*** (at the end of the luteal phase, before she starts cycling in the follicular phase)? How do they work and what are they meant to achieve?

Answer 37

**Goal: bring forward or synchronise follicular phase ** 1. **Photoperiod** - when horse is not yet cycling because days haven't started to get longer (eg., winter, November), expose to 16 hours of light to move up its oestrus by couple of months. *Works best with GnRH injections*. 2. **Progesterone** (intro & removal) - can shorten luteal phase if P4 sponge removed prior to natural oestrus but doesn't tend to be very effective unless mare is far into transition period already (like late December, early Jan) 3. **GnRH -** ***the BEST method during transition phase;*** injections or infusions mimic pulsatile pattern of secretion, inducing secretion of LH & FSH to bring forward follicular phase.

Question 38

Pharmacological interventions to control the oestrus cycle during a mare's ***breeding cycle*** (ie., follicular phase & luteal phase) are mainly to treat **fertility disorders.** What are they and what are the treatments involved?

Answer 38

**Prolonged oestrus** – treated with progesterone (PRID - progesterone releasing intrauterine device), to cause negative feedback of FSH & LH **Persistent CL** – treated with prostaglandins, specifically PGF2a, which causes luteolysis

Question 39

Aside from treating fertility problems, why would pharmacological interventions be used on mare during her breeding period (follicular & luteal phases)?

Answer 39

1. Shorten the anoestrus period after foaling 2. Synchronize oestrus in a group of mares–advantageous to get mares into oestrus in groups

Question 40

How can synchronisation of oestrus cycles be achieved through pharmacological treatment in mares?

Answer 40

1. **PGF2a** for luteolysis (decrease in P4, increase in FSH & LH, oestrus) **followed by hCG** to induce ovulation 2. **Progesterone (*allyl trenbolone*) intro & withdrawal (priming)** to mimic luteal phase then trigger move up start of oestrus cycle; follow up with **PGF2a to speed CL regression**, then use **hCG to induce ovulation**.

Question 41

What is the best way to ***induce ovulation*** in the mare during her breeding period?

Answer 41

**hCG:** In presence of a follicle \>2.5 cm, it induces ovulation in mares 24-48 after injection (mean time ~35h). - allows meiosis to resume & induces ovulation - ***follicles have no hCG receptor but hCG binds to LH receptor***

Question 42

What would be the purpose of synchronising sows?

Answer 42

To maintain a fast flow system of production by reducing the number of non-productive days. To increase the number of piglets weaned per sow per year.

Question 43

How is the sow's oestrus cycle synchronised pharmacologically?

Answer 43

**Progesterone & Gonadotrophins** **_Progesterone_**: – Oral treatment in gilts for **18 days** and sows for **5-17 days** leads to oestrus in 5-6 days after the treatment is stopped. **Disadvantages:** –This does NOT lead to reduction in non-productive days. - Also difficult to dose in group-fed animals and is **CONTRAINDICATED for pregnant animals and boars**. **_Gonadotrophins_**: Have to be used in **acyclic** sows. Safe in all physiological states. – Combination of **PMSG** and **hCG**

Question 44

What are the main distinguishing features of the bitch's oestrus cycle?

Answer 44

It's very long: 93 days After a drop in P4 by the CL in luteal phase, dog goes into long period of physiological anoestrus during which she can't go into oestrus at all. Luteal phase is very long at 75 days - almost as long as pregnancy.

Question 45

What are three ways of controlling the bitch's oestrus cycle pharmacologically or surgically?

Answer 45

1. **_Spaying_** Ovariectomy 2. _**Synthetic progesterone ****Proligestone (PRG)**_** ** "Good progesterone” designed to prevent oestrus in queens & bitches. It's ***not possible to use natural progesterone*** to extend dioestrus (luteal phase) because it’s **not active orally** and it has a **short duration of action when given parenterally**. Synthetics overcome disadvantages of natural progesterone. Proligestone is **strongly anti-gonadotrophic**, weakly progestagenic & antioestrogenic (controls vulval swelling & bleeding) _Disadvantages_**:** - first generation synthetic progesterones potentially induce GH secretion leading to ↑ risk of acromegaly, mammary tumours & diabetes mellitus 3. **_Testosterone_** Has advantage of being **active by mouth** BUT has disadvantage of affecting fertility subsequently as well as causing protrusion of clitoris and enlarging the vulva

Question 46

What are the distinguishing features of the queen's oestrus cycle?

Answer 46

The queen's oestrus cycle is variable in length. She has multiple ovulations during the follicular phase, and she is an induced ovulator. Her luteal phase is 45 days long, but her gestation period is 60 days long (this has implications for signalling maternal recognition of pregnancy). She is capable of going through a false pregnancy if mating is infertile.

Question 47

How is the queen's oestrus cycle controlled pharmacologically/surgically?

Answer 47

1. **Spaying** Ovariohysterectomy 2. **hCG** ***Induces ovulation*** & delays subsequent calling because queen goes through period of ***false pregnancy.*** **3. Androgens** Androgenic anabolic steroids used to postpone calling by giving daily oral doses ~ 30 days before anticipated oestrus _Disadvantage_: induces masculinisation **4. Progesterone** Only orally administered are suitable _Prevention_: given as soon as first calling begins; suppresses call & ovulation (prevents LH surge); prevents conception should mating occur; _Temporary postponement:_ given during anoestrus will postpone what follows naturally (oestrus) _Permanent postponement:_ repeat doses during anoestrus

Question 48

What is distinctive about the woman's oestrus cycle?

Answer 48

Follicular phase is as long as the luteal phase (14 days + 14 days). Ovulation happens mid-way through cycle. No "heat" period. In luteal phase, CL secretes oestrogen as well as progesterone.

Question 49

How is the oestrus cycle manipulated/controlled in women pharmacologically?

Answer 49

**1. GnRH** Agonists and antagonists **2. Gonadotrophins** PMSG & hCG Pure FSH & hCG **3. Gonadal steroids** _Combination oestrogen/progestrone_ - blocks sperm transport, prevents ovulation & creates a hostile uterine environment to prevent implantation _Progesterone_ - prevents ovulation; some weight gain/ possible loss of fertility once stopped – not marketed in US _Oestrogen “Morning after”_ - Acts to prevent transport of fertilized egg; slight increased risk of tubal pregnancy