Pharmacological control of reproduction Flashcards

1
Q

Label the hormonal control of reproduction in the female

A
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2
Q

Describe the hormonal regulation of the oestrous cycle in females

A

Hypothalamus releases Gonadotropin-Releasing Hormone (GnRH), which stimulates the anterior pituitary.
The anterior pituitary secretes Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH).
FSH stimulates follicular development in the ovary, leading to the release of oestrogen from the follicle.
Oestrogen acts on target tissues to induce behavioural and physiological changes for reproduction.
The growing follicle also secretes activin (enhancing FSH release) and inhibin (inhibiting FSH release).
A surge in LH triggers ovulation, forming the corpus luteum from the ruptured follicle.
The corpus luteum secretes progesterone, preparing the body for pregnancy and inhibiting further ovulation.
If no pregnancy occurs, the uterus releases prostaglandin, causing luteolysis (regression of the corpus luteum), lowering progesterone, and allowing the cycle to restart.

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3
Q

How can the female reproductive cycle be halted?

A

Give progesterone or oestrogen/testosterone (androgens) => negative feedback on hypothalamus => decreased GnRH production

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4
Q

What is the risk of controlling the reproductive cycle using progesterone or androgens in females?

A

Progesterone
- mammary enlargement and possibility of tumours
- increased risk of pyometra

Testosterone
- clitoral enlargement

Oestrogen
- cause bone marrow suppression

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5
Q

Label the hormonal reproductive control in males

A
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6
Q

What is the consequence of giving testosterone or progesterone in males?

A

-ve feedback on hypothalamus => decreased GnRH => decreased FSH and LH => gonads are not stimulated, no stimulation of spermatogenesis => tiny testicles, poor sperm quality and decreased sperm production, possible behavioural changes (cycle can be blocked in entire males to change behaviour by lowering testosterone e.g., if aggressive)

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7
Q

How can benign peri-anal adenoma in males be treated?

A

Adenomas are stimulated by testosterone

By giving progesterone => -ve feedback on hypothalamus => decreased GnRH etc => decreased testosterone production => decreased size of adenoma

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8
Q

How do GnRH agonists work?

A

Cause an initial stimulation => followed by receptor down-regulation => act as a GnRH antagonists => decreasing testosterone and sex drive

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9
Q

Why does giving GnRH, FSH or LH have a limited impact on improving fertility?

A

because we cannot mimic the way in which they are released naturally (where the amplitude and pulse frequency of concentration is important for the biological effect)

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10
Q

What is the use of exogenous GnRH and hCG (LH-like activity) in males?

A

Used to confirm the presence of functional testicular tissue - if testosterone increases after exogenous hormone = functional testicular tissue present

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11
Q

Describe the hormonal regulation of spermatogenesis in male animals.

A

Hypothalamus releases Gonadotropin-Releasing Hormone (GnRH), stimulating the anterior pituitary.
The anterior pituitary secretes Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH).
LH stimulates Leydig cells in the testes to produce testosterone, which acts on target tissues to support male reproductive function.
FSH acts on Sertoli cells, promoting spermatogenesis and the production of androgen-binding protein (ABP), which helps maintain high testosterone levels in the testes.
Sertoli cells also produce oestrogen, inhibin, and activin:
- Activin enhances FSH release.
- Inhibin inhibits FSH secretion, regulating sperm production.
Testosterone and oestrogen exert negative feedback on the hypothalamus and anterior pituitary, regulating hormone levels and preventing excessive sperm production.

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12
Q

In what ways can we pharmacologically control reproduction in females?

A
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13
Q

Why might we stimulate oestrus/ovulation?

A

For optimal/controlled mating:
- Synchronisation of a group of animals
- Induction of ovulation
- Hasten return of cyclicty (i.e. after parturition, season, lactation)

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14
Q

Why might we want to suppress oestrus/ovulation?

A

prevent breeding

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15
Q

How is oestrus/ovulation controlled?

A

Influencing photoperiod or its control (season)
Mimicking release of gonadotrophins for stimulatory or down-regulation purposes
Lengthening or mimicking the luteal phase
Blocking progesterone
Shortening the luteal phase (PGF2A or Prolactin inhibitor) - enables animal to come back into follicular phase

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16
Q

Describe the control of oestrus and ovulation in sheep

A

Stimulate onset of cyclicity earlier in breeding season:
- Melatonin
- Progestogen sponges for ~14 days in combination with ECG/GnRH
- Ram effect - ram induces female into oestrus earlier

Synchronisation of breeding for management purposes

17
Q

How does a progesterone sponge work?

A

The sponge releases progesterone, mimicking the luteal phase and preventing ovulation.
After several days (commonly 12–14 days), the sponge is removed, causing a drop in progesterone.
This triggers the animal to come into oestrus (heat) within a few days, allowing for timed breeding or artificial insemination.

18
Q

Describe control of oestrus and ovulation in pigs

A

Aid oestrus detection / management of mating

Multiple protocols e.g.
- Ovsynch (with or without P4)
- Progestogen plus PGF

May with fixed-time AI

19
Q

Describe the control of oestrus and ovulation in cattle

A

Synchronisation of a group of sows or gilts that enables batch farrowing
- Progestogen (oral) for 14-18 days with or without ECG just before P4 removal

Limited hormonal use after weaning

Two doses of PGF ineffective as CL only responsive d11-16

20
Q

What are the different hormonal control protocols in cattle?

A
  1. P4 for >7 days plus PGF
    Followed by fixed-timed AI
  2. prostaglandin => GnRH => prostaglandin => AI (Ovsynch)
  3. GnRH => progesterone device => Prostaglandin => GnRH => AI
21
Q

Describe the control of oestrus and ovulation in horses

A

Suppression of oestrus to enable training and performance
- Repeated treatment of progestogen for 10-15 days

Stimulate onset of cyclicity in early breeding season
- Daylight
- Oral progestogen for ~10 days

Management of AI/mating
- Progestogen
- PGF if active CL is present
- Hasten ovulation with HCG/GnRH

22
Q

Describe the control of oestrus and ovulation in dogs

A

Prevention of oestrus

Suppression of oestrus
- Progestogen depots for 6+ months (increased risk of pyometra if started in pro-oestrus or oestrus)
- GnRH agonist implant (takes time to act)
- Testosterone in Greyhounds

Induction of oestrus (delayed puberty / prolonged lactational anoestrus)
- Prolactin inhibitors for 2-5 weeks
- GnRH agonist implant
- HCG to induce ovulation

23
Q

Describe the control of oestrus and ovulation in cats

A

Prevention of oestrus

Suppression of oestrus
- GnRH agonist implant
-GnRH antagonists
- Melatonin implants

Induction of oestrus
- Exposure to daylight
- HCG to induce ovulation

24
Q

How can anovulatory anoestrus be resolved?

A

Make sure animals in “breeding” window to maximise chance of timely conception
Stimulate follicular development to ensure ovulatory follicle is mature
Control time of ovulation to enable use of fixed time mating
Ensure the induced CL is functionally normal

Ovsynch (GnRH-PGF-GnRH)
Ovsynch plus progestogen
Progesterone plus eCG (and/or GnRH, PGF)

25
Describe the resolution of cystic ovarian disease
Resolution of pre-disposing factors as likely to re-occur Diagnosis critical to successful treatment Luteinise if any follicular structures Suppress the hypothalamus-pituitary axis by mimicking luteal phase Stimulate luteolysis / regression of luteal tissue Follicular phase: GnRH to induce luteinisation. Followed by PGF2A i.e. Ovsynch Progestogen-based Luteal phase: PGF2A
26
Describe the resolution of persistent CL/prolonged dioestrus
Likely due to lack of endometrial PGF2A Difficult to confirm reason Make sure not pregnant PGF2A to trigger luteolysis Return to oestrus with in 2-5 days
27
Describe immuno-contraception
Vaccination against key reproductive proteins has potential to prevent conception in domestic and wild animals 2 most common targets: - zona pellucida vaccines (prevents function and therefore fertilisation) - anti-GnRH vaccines (can be used in males and females, potentially reversible)
28
Describe the treatment of pseudopregnancy/termination of pregnancy
Block action of progesterone e.g. progesterone receptor antagonist for unwanted pregnancy in dogs and cats - used in earlier stages Terminate luteal function - Prostaglandin F2α causes luteolysis (not recommended in dogs due to side effects) - Prolactin (PRL) inhibitors remove PRL-induced luteal support Mimic fetal signal e.g. corticosteroids in conjunction with prostaglandins - later stage Combination may be required