Proceedings of the Society for Theriogenology 2013 Annual Conference

www.ivis.org Proceedings of the Society for Theriogenology 2013 Annual Conference Aug. 7-10, 2013 Louisville, KY, USA www.therio.org/ Next SFT Meeting: Aug. 6-9, 2014 Portland, OR, USA Reprinted in the IVIS website with the permission of the Society for Theriogenology

Estrus synchronization in goats Lionel J. Dawson Boren Veterinary Medical Teaching Hospital, Oklahoma State University, Stillwater, OK Abstract Estrus synchronization allows breeding does in a short period of time by effectively using the bucks, or by performing artificial insemination (AI). Synchronization of the does will allow increased proportion of does becoming pregnant in a short period of time, uniform size of kids at weaning, take advantage of the niche in the market for meat during religious events and rising price trends in the market. In the past synchronization of estrus in goats has focused primarily on dairy goats to allow for optimal timing of milk production. Methods of synchronization have included techniques such as alteration of light patterns, manipulation of social interaction, buck exposure early in the breeding season and manipulating the estrous cycle by extending or shortening the luteal phase of the cycle. During the breeding season the opportunity to control the estrous cycle is greater during the luteal phase which is of longer in duration and is more responsive to manipulation. Keywords: Synchronization, estrous cycle, manipulation Introduction Goats are generally classified as a seasonally polyestrous or short day breeders in the U.S. The degree of seasonally varies among breeds and their locations (latitude). The annual reproductive cycle of goats in a temperate region can be divided into the breeding season or period, the nonbreeding season or physiologic anestrous period and the transitional period. The transitional period is between the nonbreeding and the breeding season. Estrus synchronization allows breeding does in a short period of time by effectively using the bucks, or improving the genetic make-up of the flock by performing AI. With the rapid increase in meat goats in the U.S., estrus synchronization has been used as an effective tool in the reproductive management of these herds. Synchronization early in the breeding season will allow an increased proportion of does becoming pregnant early, older and uniform size of kids at weaning, take advantage of the niche in the market during religious events and rising price trends in the market. In the past synchronization of estrus in goats has focused primarily on dairy goats to allow for optimal timing of milk production. Methods of synchronization have included techniques such as alteration of light patterns, manipulation of social interaction like buck exposure early in the breeding season and manipulating the estrous cycle by extending or shortening the luteal phase of the cycle. During the breeding season the opportunity to control the estrous cycle is greater during the luteal phase which is of longer in duration and is more responsive to manipulation. Strategies can be employed for synchronization, is to extend the luteal phase by supplying exogenous progesterone or to shorten this phase by prematurely regressing the existing corpus luteum (CL) by using prostaglandin. 1-7 Hormones have been used in goats to manipulate the estrous cycle, but none have been approved for use in goats in the U.S. Discussion Extending the luteal by supplying exogenous progesterone is best done by using controlled internal drug release devices (CIDR), intravaginal sponges and feed supplements. 2 Regressing or lysing the CL is best done by utilizing prostaglandin. Progesterone or progestagens products commonly used are CIDR s and sponges (Veramix, Repromap, Sincrocel, Cronolone and Chronogest). Shortening the luteal phase is best done by using dinoprost tromethamine and cloprostenol. 1-7 For better control or synchrony of estrus and ovulation, extending the luteal phase with progesterone, along with a gonadotropin (follicle stimulating hormone; FSH) and prostaglandin have been used. The gonadotropin commonly used is equine chorionic gonadotropin (ecg) because of its longer half-life. The drawback of using higher doses ecg may result in a larger number of anovulatory follicles Clinical Theriogenology Volume 5, Number 3 September 2013 270

and repeated doses can cause declining fertility due to the buildup of antibodies against ecg. 7-8 Equine chorionic gonadotropin is not commercially available in the U.S. but a product containing ecg and human chronic gonadotropin (hcg) which has been labeled to be used in swine (PG 600; Intervet Inc, Merck Animal Health, Summit, NJ) for induction estrus in gilts has been tried and used in goats. The dosage of PG 600 utilized in does is 200 units of ecg + 100 units of hcg (1/2 dose) during the breeding season or 400 units of ecg + 200 units of hcg (full dose) during the non-breeding or off season. If ecg is used, the dose is 200 units of ecg during the breeding season and 400 units of ecg during the nonbreeding or off season. During the transitional period (late July to early September), buck effect is a powerful tool to induce estrus (Table1). Sudden introduction of previously isolated bucks will stimulate a surge of luteinizing hormone (LH) followed by ovulation and majority of the does exhibit estrus within 48-72 hours. 1,3,9-11 Thirty to 60% of does will show estrus behavior and ovulate within 3-5 days or 7-12 days after introduction of the buck. Three peaks of estrus activity have been observed, after the introduction of the buck, 3-5 days, 7-12 days and 28 to 35 days after introduction to the buck. 9 This phenomenon of cycling in seven to 12 days is described as early luteal regression (ELR). 3,4,7-14 The current thinking is that ELR maybe due to lack of progesterone priming of the uterus during the anestrus and early transition periods. Estrogen produced by the follicles at that time will have a positive effect on the uterus. Estrogen increases the availability of oxytocin receptors leading to the release of endogenous prostaglandin and thereby lysing the CL. Does that were supplemented with progesterone in late-transition which was removed on the day the bucks were introduced had higher percentage showing estrus and reduced the number of short cycles. Buck effect and exogenous progesterone are methods commonly employed to induce estrus in the transition period and to prevent ELR (Table1). 12-14 Out of season breeding in does could be done by using hormones or manipulating the photoperiod to hasten the onset of estrus. Out of season breeding will enable the producer to take their kid crop to market when prices are higher, have year round milk production in dairy animals and also increase the number of kids born to the doe during her lifetime. Hormones are commonly used effectively to synchronize estrus in this period. Incorporating FSH into the protocol is essential to stimulate follicular waves during the nonbreeding season or off season. Equine chorionic gonadotropin is commonly used in the U.S. PG 600 which contains ecg is available in the U.S. and has been used successfully used in goats (Table 2). Photoperiod manipulation is done by altering the day length. Decreasing day length will increase the levels of melatonin produced by the pineal gland. Melatonin production may influence the secretion of LH from the anterior pituitary gland and hasten cyclicity. 25-38 Melatonin will increase the pulsatile release of gonadotropin releasing hormone (GnRH), thereby increasing the frequencies of FSH and LH release. Increased levels of LH release will cause ovulation, and thus enabling doe to cycle regularly. Change in light exposure or decreasing day length requires at least 45-60 days to induce a doe to cycle. Gradual change is not necessary; the amount of change that is perceived by the eye is important. A reduction of light is effective to trigger estrus activity in 30 to 60 days in a doe. 19,24,39,40 Exogenous melatonin can be administered to supplement endogenous release and thereby mimic short days associated with the breeding season. 19,24,39,40 Melatonin is more effective in advancing the breeding season than inducing or initiating it and is more effective if melatonin is given after the doe is exposed to long days. There are numerous protocols for synchronizing the estrous cycle in a doe have been used and described in the literature. Protocols 1 and 2 have been utilized by the author in various clinical trials at the American Institute for Goat Research at Langston University. For AI involving transcervical or laparoscopic insemination protocol 2 with timed AI has been used with good success. Dr. Nutti, a reproductive physiologist at Prairie View A&M, has utilized protocols 4 to 6 in conducting AI workshops in the U.S. and other countries where different pharmaceutical agents were not readily available. Prostaglandin by itself is used primarily during the breeding season to synchronize estrus in does. 271 Clinical Theriogenology Volume 5, Number 3 September 2013

Table 1. Methods employed to hasten estrus activity during the transition period Method Duration Estrous 1.Buck effect Late transition 24-96 hours 2. Progesterone(12-14 days) + equine chorionic gonadotropin(ecg) on the day or 24-48 hours prior to removal 3. Progesterone(12-14days) + ecg on the day or 24 to 48 hours prior to removal 4. Progesterone(10days) +ecg(removal) +prostaglandin 48 hours prior to removal This table is adapted from Current therapy in large animal theriogenology Early transition Late transition Late transition 24-72 hours 24-48 hours 40.9+- 3.2 hours Table 2. Methods employed during the non-breeding season Method Duration Estrus Progesterone 12-14 days 24-96 hours 1,2,3 +Equine Chorionic Gonadotropin On the day of removal or 24-48 hours before +Prostaglandin On the day of removal or 24-48 hours before 44.6 + 8.2 hours 15 25 + 5 hours 8,16-18 <72 hours - 90% in estrus Artificial lights Mimic long days for 60 days followed by short days for 60 days or natural light 40-70 days during short days 19 Melatonin (Implant, oral, or injection) 60-100 days 30-60 days 40 Artificial lights + melatonin Mimic long days for 60 days followed by melatonin for 60-100 days Buck exposure 60 days into melatonin treatment; estrus 2-3 days 24 Common synchronization of protocols used in does Clinical Theriogenology Volume 5, Number 3 September 2013 272

1. CIDR/ Lutylase 0 5 10 12 13 Insert CIDR NS or A.I.= 24 hours after standing estrus TAI= 52 to 56 hours after CIDR removal Removed 5-10mg Dinoprost tromethamine (1-2cc Lutylase) 273 Clinical Theriogenology Volume 5, Number 3 September 2013

2. CIDR + PG 600 +Lutylase 0 5 10 12 13 Insert CIDR NS or A.I =24 hours after standing estrus TAI = 42 to 48 hours after CIDR removal 5-10mg Dinoprost tromethamine (1-2cc Lutylase) Remove CIDR Give 5cc PG600 during the off season ½ dose during the breeding season (400 units ecg and 200 units HCG) 3. CIDR+eCG+Lutylase 0 5 10 12 13 Insert CIDR NS or A.I.= 24 hours after standing estrus TAI=52-54 hours after CIDR removal 5-10mg Dinoprost tromethamine (1-2cc Lutylase) Remove CIDR 4cc ecg (400 units ecg) during the off season- 1/2 dose during the breeding Clinical Theriogenology Volume 5, Number 3 September 2013 274

4. Select Synch & CIDR 0 7 7-12 GnRH PGF2 HD & AI CIDR(in) Remove CIDR 5. Select Synch/CIDR/TAI 0 7 10 CIDR (in) + GnRH CIDR(out) + PGF TAI at 72 hours 6. Select Synch/CIDR/TAI/GnRH 0 7 7-10 10 GnRH CIDR PGF2 Remove CIDR GnRH-50 micrograms HD & AI for 72 hrs 72 hours TAI & GnRH 7. Shortening the luteal phase Product Dosage Treatment Route Estrus Lutalyse (Dinoprost tromethamine) 5-10 milligrams 2 injections, 11 to 12 days apart in does l/m 24-72 hours (48-60 hours) TAI + 50-52 hours (Cloroprostenol) 50-150 micrograms 2 injections, 11 to 12 days apart l/m 24-72 hours (48-60 hours) TAI=50-52 hours 8. Two injections of prostaglandin = Heat detection two periods HD & Al or NS (48-72hrs) HD & Al or NS (48-7hrs) 0 Lutylase or 3 Inject the ones not in estrus on 11 or 12 Lutylase Or s 13-15 275 Clinical Theriogenology Volume 5, Number 3 September 2013

9. Two injections of prostaglandin = Heat detection one period HD & Al or NS (48-72hrs) 0 Lutylase Or 11 or 12 Lutylase Or HD & Al 10. Heat detection and prostaglandin With teaser bucks-remove the does to breed from day 1 to 5 HD & Breed from D6-9 (Al or NS) 0 6 Rest of the does Lutylase Or 9 Clinical Theriogenology Volume 5, Number 3 September 2013 276

11. Event Prairie View A&M Langston #1 Langston #2 North Carolina CIDR In for 7 days In for 10-14 days In for 6 days Not used Prostaglandin (Lutalyse) 1 ml given 3 days before anticipated AI and at time of pulling CIDRs 2ml given 24 hours before pulling CIDRs 2 ml given with placing of CIDRs 2 ml given at days 0 and 14 GnRH(Cystorelin) 1 ml given with placing of CIDRs Not used Not used 1 ml given at days 7 and 17 PMSG/eCG(PG-600) Not used 2.5 ml(half-dose) given at the time of pulling CIDRs 2.5ml (half dose) given at the time of pulling CIDRs Not used Diagram CID R(in )+G nrh CID R (out ) + PGF IA CID R(in ) PG F CIDR (out) + IA PMS G CI DR (in )+ PG CI DR (o ut) +e IA PG F G n PG F Gn RH +IA 0 7 10 0 9 10 12 0 6 8 0 7 14 17 Summary There has been rapid progress during the last decade in the U.S. toward manipulating the estrus cycle in does. With the availability of CIDRs in the U.S and approval for use in sheep, data have been collected by Iowa State University regarding approval for use in goats. Prostaglandin, PG 600, GnRH and CIDRs are not approved for use in goats. They have been used in an extra-label manner and the practitioner should be aware that under AMUDUCA regulations non-therapeutic extra-label use is not permitted. Thus regulatory guidance should be requested in use of these products in goats. References 1. Dawson LJ: Manipulating the estrous cycle in a doe. In: Youngquist RS, Threlfall WR, editors. Current therapy in large animal theriogenology. 2nd ed. St. Louis: Saunders; 2007. p. 540-546. 2. Wildeus S: Current concepts in synchronization of estrus: sheep and goats. Proc Am Soc Anim Sci; 1999-2000. p. 1-9. 3. Whitley NC, Jackson DJ: An update on estrus synchronization in goats: a minor species. J Anim Sci 2004;82(E Suppl):E270-276. 4. Bretzlaff K: Control of the estrous cycle. In: Youngquist RS, editor. Current therapy in large animal theriogenology. Philadelphia: Saunders; 1997. p. 510-514. 277 Clinical Theriogenology Volume 5, Number 3 September 2013

5. Keisler DH, Buckrell BC: Breeding strategies in ewes. In Youngquist RS, editor. Current therapy in large animal theriogenology. Philadelphia: Saunders; 1997. p. 603-611. 6. Buckrell BC: Hormonal management of breeding in sheep and goats. Proc Small Ruminant Short Course (ACT and SFT); 1994. p. 32-40. 7. Pugh DG: Female reproduction in the ewe and doe. In: Sheep and goat medicine. Philadelphia: Saunders; 2002. p. 147 8. Baril G, Remy B, Leboeuf B, et al: Synchronization of estrus in goats. The relationship between ecg binding in plasma, time of occurrence of estrus and forcibly following artificial insemination. Theriogenology 1996;45:1553-1559. 9. Chimineau P: Possibilities for using bucks to stimulate ovarian and estrous cycles in anovulatory goats a review. Livestock Prod Sci 1987;17:135-147. 10. Ott RS, Nelson DR, Hixon JE: Effect of presence of the male on initiation of estrus cycle activity of goats. Theriogenology 1980; 13:183-190. 11. Mellado M, Olivas R, Ruiz F: Effect of buck stimulus on mature and pre-pubertal norgestomet treated goats. Small Rum Res 2000;36:269-274. 12. Beard AP, Hunter MG: Effects of bovine follicular fluid and exogenous estradiol on the GnRH induced short luteal phase in anestrus ewes. J Reprod Fertil 1994;100:211-217. 13. Baltye HM, Fairclough RJ, Cameron AWN, et al: Evidence for prostaglandin involvement in early luteal regression of the superovulated nanny goat. J Reprod Fertil 1988;84:425-430. 14. Chimenineau P: Effects of a progestogen on buck induced short ovarian cycles in the Creole meat goat. Anim Reprod Sci 1985;9:87-94. 15. Zarkawi M, Al-Merestani MR, Wardeh MF: Induction of synchronized oestrous in indigenous Damascus goats outside the breeding season. Small Rumin Res 1999;33:193-197. 16. Leboeuf B, Forgerit Y, Bernelas D, et al: Efficacy of two types of vaginal sponges to control onset of oestrus, time of preovulatory LH peak and kidding rate in goats inseminated with variable number of spermatozoa. Theriogenology 2003;60:1371-1378. 17. Freitas VJF, Baril G, Saumande J: Estrus synchronization in dairy goats in use of fluorogestone acetate vaginal sponges or norgestomet ear implants. Anim Reprod Sci 1997;46:237-244. 18. Freitas VJF, Baril G, Bose M, et al: The influence of ovarian status response to estrus synchronization treatment in dairy goats during the breeding season. Theriogenology 1996;45:1561-1567. 19. BonDurant RH, Darian BJ, Munvo CJ, et al: Photoperiod induction of fertile oestrus and changes in LH and progesterone concentration in yearling dairy goats. J Reprod Fertil 1981;63:1-9. 20. Shelton M: Reproduction and breeding of goats. J Dairy Sci 1978;31:994-1010. 21. East NE, Rowe JD: Subcutaneous progestin implants verses intra vaginal sponges for dairy goats estrus synchronization during the transitional period. Theriogenology 1989;32:921-928. 22. Dawson LJ: Estrus synchronization in does. Proc Small Rumin Reprod. Kansas State University; 2011. 23. Pierson JT, Baldassarre H, Keefer CL, et al: Seasonal variation in preovulatory events associated with synchronization of estrus in dairy goats. Theriogenology 2001;56:759-769. 24. Chimeneau P, Normant E, Ravault JP, et al: Induction and persistence of pituitary and ovarian activity in the out-ofseason lactating dairy goat after a treatment combining a skeleton photoperiod, melatonin and the male effect. J Reprod Fertil 1986; 78:497-454. 25. Amoah EA, Gelaye S, Guthrie P, et al: Breeding season and aspects of reproduction of female goats. J Animal Sci 1996;74:723-728. 26. Keisler DH: Endocrine control of reproduction in the ewe and ram. Proc Small Anim Rumin Short Course (ACT and SFT); 1994. p. 2-31. 27. Lincoln GA, Short RV: Seasonal breeding: nature s contraceptive. Recent Prog Horm Res 1980;36:1-43. 28. Karsch FJ: The hypothalamus and anterior pituitary gland. In: Austin CR, Short RV, editor. Reproduction in mammals: hormone control of reproduction. Cambridge: University Press; 1984. p. 1-20. 29. Goodman RL, Karsch FJ: The hypothalamic pulse generator: a key determinant of reproductive cycles in sheep. In: Follett BK, Follett DE, editors. Biological clocks and seasonal reproductive cycles. Bristol: John Wright Pub; 1981. p. 223-242. 30. Thiery JC, Pelletier J: Multiunit activity in the anterior median eminence and adjacent areas of the hypothalamus of the ewe in relation to LH secretion. Neuroendocrinology 1981;32:217-224. 31. Clarke IJ, Cummins JT: The temporal relationship between gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) recreation in ovariectomized ewes. Endocrinology 1982;111:1737-1739. 32. I Anson H, Herbosa CG, Ebling FJ, et al: Hypothalamic versus pituitary stimulation of luteinizing hormone secretion in the prepubertal female lamb. Neuroendocrinology 1993;57:467-475. 33. Jansen HT, Khalid M, Jackson GL: N-Methyl-D,L-aspartate induces a transient increase in LH secretion in the seasonally anestrous ewe. Domest Anim Endocrinol 1991;8:55-62. 34. Kinder JE, ML, Kittok RJ: Endocrine regulation of puberty in cows and ewes. J Reprod Fertil (Suppl) 1987;34:167-186. 35. Karsch FJ, Goodman RL, Legon SJ: Feedback basis of seasonal breeding: test of an hypothesis. J Reprod Fertil 1980; 58:521-535. Clinical Theriogenology Volume 5, Number 3 September 2013 278

36. Moss GE, Crowder ME, Nett TM: GnRH-receptor interaction. VI. Effect of progesterone and estradiol on hypophyseal concentrations of gondaotrophins in ovariectomized ewes. Biol Reprod 1981;25:938-944. 37. Reeves JJ, Arimura A, Scally AV: Changes in pituitary responsiveness to luteinizing-hormone, releasing hormone (LH- RH) in anestrous ewes pretreated with estradiol benzoate. Biol Reprod 1971;4:88-92. 38. Moenter SM, Caraty A, Lacatelli A, et al: Pattern of gonadotrophin-releasing hormone (GnRH) secretion leading up to ovulation in the ewe: existence of a preovulatory GnRH surge. Endocrinology 1991;129:1175-1182. 39. VonBrackel-Bodenhauser A, Wuttke W, Holtz W: Effects of photoperiod and slow-release preparations of bromocriptine and melatonin on reproductive and prolactin secretion in female goats. J Anim Sci 1994;72:955-962. 40. Wuliji T, Litherland A, Goetsch AL, et al: Evaluation of melatonin and bromocryptine administration in Spanish goats. Small Rumin Res 2003;49:41-49. 279 Clinical Theriogenology Volume 5, Number 3 September 2013