The use of exogenous hormones to control estrus

in horses.

Dr. Dhiren B. BhoiM.V.Sc., (Gynaecology)

Learning Objectives

• Reasons why we use hormones for equine reproduction

• Accelerating the transition period

• Initiate ovulation

• Manipulate luteolysis

• Overall schedule exogenous hormones

• Which are best?

Reasons to Establish Controlled Cycles(Pre-determined Schedule)

• The physiologic breeding season: April to Late Summer• Use in absence of a teasing stallion

– Unavailable stallion, difficult to detect heat

• Predicted stallion collection, shipping times• Shorten stays at a breeding farm • Cooled semen shorter life• Decreased handling/efforts, optimize fertility, early foals

for performance• COST/PROFIT$$$

Unique Species• Seasonally polyestrus (long day)

• Ovarian Physiology: Ovulation occurs at a single spot,• “Ovulation Fossa”

• Unlike other farms species, most mares have only one follicular wave – Proestrus phase is the shortest of all farm species

Estrous cycle 21d

Estrus duration 7d

Onset of estrus to ovulation 5d

LH surge to ovulation 2d

Senger, 2003.

Transition Period

• Period of cessation of seasonal anestrus leading to the breeding season

• Presence of multiple small non-ovulatory follicles

• Applications only speed up period; not eliminate– Lighting– GnRH– Progestins– Progestins + Estrogen– eFSH

Transition Period

[# Follicles]

[Follice Size]

[FSH]

[LH]

Donadeu, Ginther, 2002a.

Accelerating the Transition Period*Use a lighting system

Initiates transition period (10-12 wks earlier) FSH levels rise 2 months before the breeding season Caution: Absence of FSH&LH are necessary to trigger initiation

of transition period

Using Progestins (P4-like Hormones)

Suppress GnRH secretion- allows a rebound of LH secretion after the P4 tx is stopped

Mares must be well into transition period to respond (22mm)

Decreases prolonged estrus and anovulation

Complications with Progestins

•(Typically) only one follicular wave

•After the last tx of P4, size of dominant follicle could be small or large

Synchronization dependent on development of follicle

•Spontaneous ovulations during luteal phase

Good info less relevant for the assignment

Progestins

• May also be used to:

– Suppress heat in show mares– Prolong diestrus period to accommodate

stallion collection schedule

Inducing Ovulation

• Why do we need to control time of ovulation?

• Touch on different approaches – don’t need too much detail

Inducing Ovulation

*hCG (Human Chorionic Gonadotropin)

• Large glycoprotein hormone produced by the human placenta

• LH-like: binds to equine LH receptors in ovary for LH peak

• More effective and safer late in transitional period (antibodies)

• Low cost and high clinical effectiveness

Inducing OvulationGnRH Synthetic Agonist

”Ovuplant” implant or new injectable form

• Stimulate release of LH and FSH for ovulation• Ovuplant is placed under the skin

• Use when hCG antibodies are present or a history of hCG

failure

Both hCG and GnRH achieve an ovulation within 48 hours on a 30-45mm follicle-(on ~90% of all mares)

Inducing OvulationeFSH Bioniche (Equine Pituitary Extract)

• Contains LH and FSH

• Stimulate follicular development and advance ovulation in:

– Transitional (shorten period), acyclic & superovulate cycling mares

• Give 5-7days after last ovulationGive for 3-5 days (or until follicles are >35mm)

give hCG / GnRH 36h after last eFSH to induce ovulation

• Limited availability, expensive

PGF2a

• IM Injection

• Luteolysis= binding of PGF2a to the CL during diestrus period

• Since luteal phase of cycle is short, effective PGF2a shot must be given when CL is at least day 6 of luteal phase for luteolysis to occur

• Given during the single follicular wave= regression of the CL– Synchronize cycles (for breeding or embryo transfer)

– Shortens up the luteal phase: sooner ovulation• Ovulation times can still vary significantly

• Immediate increase in LH and FSH and decrease P4

• Side effectsGood info less relevant for the assignment

PGF2a

Prostaglandin Failure (may need a 2nd tx):

• 25-30% of all mares can may exhibit 2 follicular waves– Luteolysis will occur, but large follicles in the ovaries don’t respond

• Follicle present during diestrus is almost mature, onset of estrus is rapid and ovulation is not observed– Masks the original CL lysis: gives impression that PG tx has failed– PG may be strong enough to cause an LH surge leading to ovulation

before luteolysis has occurred

Should always ultrasound to determine true

follicle size for best results

Bringing it all Bringing it all

together…together…

Brief explanation of synchronization protocols as they pertain to the mares unique physiology would be adequate

Control of estrus is the basis of predictable control of ovulation.

PGF2α PGF2α (hCG)hCG

Day 1 6 14 18 20 22

estrus

PGF2a Luteolysis of small CLhCG Ovulate any remaining large follicles 2nd PGF2a Luteolysis of new CL (may speed up luteal phase)

estrus ~3-4d later2nd hCG LH surge to induce ovulation 48hours later (>30mm)

Breed: At ovulation or within 48-72 hours before (time of hCG shot) Dependent on breeding method or shipment timing

Breed

Use this method in conjunction with ultrasound to determine follicle sizeUse as an alternative to progestin treatment when prolonging of the luteal phase is not desired or mare is out of transition period

Novak, 2007

PGF2α Progesterone hCGovulation

Day 1 12 16 18 21

Day 1 8 12 14 16

estrus

Breed

Novak, 2007

•P4 : Given for no more than 15 days •Mare must have some follicular activity (20mm)ie, Lighting system•Removal will initiate GnRH to stimulate LH release

•PGF2a: Given on last day of P4 tx•Luteolysis of remaining CL’s•Mares will come into heat ~3-4 days later

•hCG: LH surge to induce ovulation 48hours later (>30mm)Breed: At ovulation or within 48-72 hours before (time

of hCG shot) Use this method after a period of light stimulation for adequate follicular development to shorten the transition period and calm gonadotropin secretion

for a period when the cycle timing (breeding) needs to be controlled

Suggested for insemination of mares when more than one dose is available:

•Daily examinations during estrus (any time)•Day 0 Day of 35 to 40 mm follicle detection•Administer hCG or deslorelin at approximately 4:00 PM•Day 1 Inseminate a single dose of frozen semen at 4:00 PM (24 hrs post-injection).•Day 2 Inseminate a second dose of frozen semen at 8:00 AM (40 hours post-injection).•Day 3 Examine to confirm ovulation & inseminate 3rd dose if the mare has not ovulated @8AM

www.selectbreeders.com

Selection of a specific agent may be based on:

• Cost

• Efficacy

• Time of year

• Age of the mare

• Follicle size

• Previous use or success

• Clinician preference.

Touch on these – don’t need too much details

• Lofstedt R. 2004. Rational uses of hormones in broodmares. Professor of Theriogenology Atlantic Vetereinary College.

• Lofstedt. R. 2003. The use of progesterone & estradiol in broodmares.

• Donadeu, F.X., Ginther, O.J., 2002a. Follicular waves and circulating concentrations of gonadotrophins, inhibin and oestradiol during the anovulatory season in mares. Reproduction 124, 875–885.

• McCue, P.M., et al. 2006. Comparison of Compounded Deslorelin and hCG for Induction of Ovulation in Mares. Elsevier www.sciencedirect.com. Theriogenology 68.

• McCue, P.M., et al. 2007. eFSH in clinical equine practice. Elsevier www.sciencedirect.com. Theriogenology 68:429–433

• Management of Mares for Frozen Semen Insemination. www.selectbreeders.com• Douglas RH, Ginther OJ. Effect of prostaglandin F2alpha on length of diestrus in

mares.Prostaglandins. 1972 Oct;2(4):265-8. No abstract available. PubMed - indexed for MEDLINE

• http://www.utextension.utk.edu/publications/animals/EquineFacts/TNH1004.pdf– Good summary Factsheet (modern equine Breeding Factsheet)

• Senger P.L. 2003. Pathways to pregnancy and Partuition Second Revised Edition. Pullman, WA: Current Conceptions Inc. Ch8

• Donadeu F.X., Watson E.D. 2006. Seasonal changes in ovarian activity: Lessons learnt from the horse. Animal Reproduction Science. Elsevier 100: 225-242

• McCue P.M., et al. 2007. Comparison of Compounded Deslorelin and hCG for Induction of Ovulation in Mares. Journal of Eqine Veterinary Science. Pg 58-9.

• Crowell-Davis S.L. 2007. Sexual behavior of mares. Hormones and Behavior. www.elsevier.com 52:12-17.