绵羊和山羊免疫去势及其动物福利的研究进展

doi:10.1016/S2095-3119(21)63670-5

摘要/Abstract

摘要：

雄性动物去势是畜牧行业中一种常见的做法，目的是减少动物的攻击性行为、防止异味和控制繁殖。多年来，机械去势和手术去势被广泛应用于动物绝育。然而，这些去势方法会给动物带来疼痛和恐慌，影响动物福利。最近，针对下丘脑-垂体-性腺（HPG）轴的免疫去势被认为是传统去势的有效替代方法，避免了传统去势技术的许多缺点。一般来说，它是有效的、安全的，对动物友好，适用于所有阶段的动物。然而，目前还没有关于绵羊和山羊免疫去势的最新资料。因此，本篇综述概括了从传统手术去势到免疫去势的发展历程，比较了传统去势技术与免疫去势技术的优缺点，并总结了免疫靶标的筛选过程。功能性去势以HPG轴上的激素、基因和受体为靶标，开发针对它们的免疫去势疫苗。位于HPG轴上游的靶点，如吻素（KISS1）和促性腺激素释放激素（GnRH），已被证明能有效地降低性激素水平和抑制生殖功能。因此，开发绵羊和山羊的商业去势疫苗应通过使用HPG轴上的上游来开发。另外，本文还综述了近年来绵羊和山羊免疫去势的特点、应用及福利等方面的研究进展。总之，这篇综述为绵羊和山羊免疫去势作为手术去势的替代方法提供了有用信息。

Abstract: Castration of male animals is a common practice in the meat industry aimed at reducing aggressive behavior, preventing unpleasant flavor, and controlling undesirable breeding. For many years, mechanical castration and surgical castration have been practiced to sterilize the animals. However, these castration methods are not humane because of the associated risk of death, pain, and stress. Recently, immunocastration targeting the hypothalamic-pituitary-gonadal axis (HPG) axis has been reported as an animal-friendly approach that circumvents many of the concerns with conventional castration, and suggested by researches as an alternative to surgical castration. However, there is no compilation of updated information on the use of immunocastration in sheep and goats. Therefore, this review aims to summarize the developmental process from traditional surgical castration to immunocastration and to screen the process of immune targets. It also compares the respective advantages and disadvantages of traditional castration technologies and immunocastration, in particular including analyses in the characteristics, features application and welfare benefits of immunocastration in sheep and goats were also analyzed.

Key words: immunocastration , reversibility , safety , animal welfare , DNA vaccine

. 绵羊和山羊免疫去势及其动物福利的研究进展 [J]. Journal of Integrative Agriculture, 2022, 21(2): 299-309.

ZENG Fan-mei, DING Yi, Teketay WASSIE, JING Hai-jing, Sohail AHMED, LIU Gui-qiong, JIANG Xun-ping. Recent advances in immunocastration in sheep and goat and its animal welfare benefits: A review[J]. Journal of Integrative Agriculture, 2022, 21(2): 299-309.

参考文献

Berlin F S. 2009. Commentary: Risk/benefit ratio of androgen deprivation treatment for sex offenders. Journal of the American Academy of Psychiatry and the Law Online, 37, 59–62.
Bonneau M, Weiler U. 2019. Pros and cons of alternatives to piglet castration: Welfare, boar taint, and other meat quality traits. Animals, 9, 884.
Bowen R A. 2008. Male contraceptive technology for nonhuman male mammals. Animal Reproduction Science, 105, 139–143.
Bretschneider G. 2005. Effects of age and method of castration on performance and stress response of beef male cattle: A review. Livestock Production Science, 97, 89–100.
Brunius C, Zamaratskaia G, Andersson K, Chen G, Norrby M, Madej A, Lundström K. 2011. Early immunocastration of male pigs with Improvac® - Effect on boar taint, hormones and reproductive organs. Vaccine, 29, 9514–9520.
Čandek-Potokar M, Škrlep M, Zamaratskaia G. 2017. Immunocastration as alternative to surgical castration in pigs. Theriogenology, 6, 109–126.
Caraty A, Smith J T, Lomet D, Ben Said S, Morrissey A, Cognie J, Clarke I J. 2007. Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology, 148, 5258–5267.
Catin S. 1976. Delayed effects of in vivo LHRH immunoneutralization on gonadotropins and prolactin secretion in the female rat. Endocrinology, 98, 1539–1549.
Coetzee J F, Nutsch A L, Barbur L A, Bradburn R M. 2010. A survey of castration methods and associated livestock management practices performed by bovine veterinarians in the United States. BMC Veterinary Research, 6, 12.
Cohen R D H, King B D, Hunter P S W, Janzen E D. 1991. Efficacy of chemical castration and effects of age at castration and implant regime on growth rate, testicular measurements and testosterone levels of beef calves. Canadian Journal of Animal Science, 71, 1–11.
Daniela S, Sonia V, Rafael S, Rodolfo P, Francisco C, Lisette L, Mario M, Oliver P, Leonardo S. 2016. Effectiveness of an immunocastration vaccine formulation to reduce the gonadal function in female and male mice by Th1/Th2 immune response. Theriogenology, 86, 1589–1598.
Decourt C, Robert V, Anger K, Galibert M, Madinier J B, Liu X, Herbison A E. 2016. A synthetic kisspeptin analog that triggers ovulation and advances puberty. Scientific Reports, 6, 26908.
D’Occhio M J, Gifford D R, Hoskinson R M, Weatherly T, Flavel P F, Mattner P E, Setchell B P. 1987. Reproductive hormone secretion and testicular growth in bull calves actively immunized against testosterone and oestradiol-17β. Reproduction, 79, 315–324.
D’Souza S S, Selmin F, Murty S B, Qiu W, Thanoo B C, DeLuca P P. 2004. Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist. Aaps PharmSci, 6, 94–99.
Duncan I J H. 1993. Welfare is to do with what animals feel. Journal of Agricultural & Environmental Ethics, 6, 8–14.
Earl E R, Waterston M M, Aughey E, Harvey M J, Matschke C, Colston A, Ferro V A. 2006. Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs. Vaccine, 24, 3172–3183.
European Commission. 2019. Study establishing best practices on the production, the processing and the marketing of meat from uncastrated pigs or pigs vaccinated against boar taint (immunocastrated). Standing Committee on Plants, Animals, Food and Feed. [2019-02-25]. https://ec.europa.eu/food/sites/food/files/animals/docs/reg-com_ahw_20190225_study-meat-uncas-immunocas.pdf
Fagundes A K F, Oliveira E C, Tenorio B M, Melo C C, Nery L T, Santos F A B, Silva Jr V A. 2014. Injection of a chemical castration agent, zinc gluconate, into the testes of cats results in the impairment of spermatogenesis: A potentially irreversible contraceptive approach for this species? Theriogenology, 81, 230–236.
Fang F, Li H, Liu Y, Zhang Y, Tao Y, Li Y, Zhang X. 2010. Active immunization with recombinant GnRH fusion protein in boars reduces both testicular development and mRNA expression levels of GnRH receptor in pituitary. Animal Reproduction Science, 119, 275–281.
Fordyce G, Beaman N J, Laing A R, Hodge P B, Campero C, Shepherd R K. 1989. An evaluation of calf castration by intra-testicular injection of a lactic acid solution. Australian Veterinary Journal, 66, 272–276.
Fraser H M, Gunn A. 1973. Effects of antibodies to luteinizing hormone-releasing hormone in the male rabbit and on the rat oestrous cycle. Nature, 244, 160–161.
Fredriksen B, Johnsen A M S, Skuterud E. 2011. Consumer attitudes towards castration of piglets and alternatives to surgical castration. Research in Veterinary Science, 90, 352–357.
Garside D, Gebril A, Alsaadi M, Ferro V A. 2014. Fertility control in wildlife: Review of current status, including novel and future technologies. Reproductive Sciences in Animal Conservation, 753, 467–488.
Godfrey S I, Walkden-Brown S W, Martin G B, Speijers E J. 1996. Immunisation of goat bucks against GnRH to prevent seasonal reproductive and agonistic behaviour. Animal Reproduction Science, 44, 41–54.
González L, Schwartzkopf-Genswein K, Caulkett N, Janzen E, McAllister T, Fierheller E, Schaefer A, Haley D, Stookey J, Hendrick S. 2010. Pain mitigation after band castration of beef calves and its effects on performance, behavior, Escherichia coli, and salivary cortisol. Journal of Animal Science, 88, 802–810.
Gökdal Ö, Atay O, Ülker H, Kayaardı S, Kanter M, DeAvila M D, Reeves J J. 2010. The effects of immunological castration against GnRH with recombinant OL protein (ovalbumin-LHRH-7) on carcass and meat quality characteristics, histological appearance of testes and pituitary gland in Kvrck male lambs. Meat Science, 86, 692–698.
Han X, Gu L, Xia C, Feng J, Cao X, Du X, Song T. 2015. Effect of immunization against GnRH on hypothalamic and testicular function in rams. Theriogenology, 83, 642–649.
Han Y, Liu G, Jiang X, Ijaz N, Tesema B, Xie G. 2015. KISS1 can be used as a novel target for developing a DNA immunocastration vaccine in ram lambs. Vaccine, 33, 777–782.
Han Y, Liu G, Jiang X, Xiang X, Huang Y, Nie B, Tesema B. 2018. Reversibility and safety of KISS1 metastasis suppressor gene vaccine in immunocastration of ram lambs. Asian-Australasian Journal of Animal Sciences, 31, 835–841.
Han Y, Ye W, Liu G, Jiang X, Ijaz N, Zhao J, Tesema B. 2016. Hepatitis B surface antigen S gene is an effective carrier molecule for developing GnRH DNA immunocastration vaccine in mice. Reproduction in Domestic Animals, 51, 445–450.
Hobernik D, Bros M. 2018. DNA vaccines - how far from clinical use? International Journal of Molecular Sciences, 19, 3605–3633.
Hötzel M J, Caraty A, Martin G B. 1997. Effects of nutrition on testicular growth in mature Merino rams actively immunized against GnRH. Reproductive Fertility, 110, 307–313.
Janett F, Lanker U, Joerg H, Hässig M, Thun R. 2003. The castration of male lambs by immunization against GnRH. Schweizer Archiv für Tierheilkunde, 145, 291–299.
Karaku F, Yilmaz A, Hakan B, Stormo K, Ulker H. 2013. The effectiveness of recombinant OL fusion protein (ovalbumin-LHRH-7) in suppressing reproductive functions when injected in single-dose vaccination protocols with different adjuvants. Animal Reproduction Science, 138, 228–232.
Killian G, Miller L, Rhyan J, Doten H. 2006. Immunocontraception of Florida feral swine with a single-dose GnRH vaccine. American Journal of Reproductive Immunology, 55, 378–384.
Kiyma Z, Adams T E, Hess B W, Riley M L, Murdoch W J, Moss G E. 2000. Gonadal function, sexual behavior, feedlot performance, and carcass traits of ram lambs actively immunized against GnRH. Journal of Animal Science, 78, 2237–2243.
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J M, Le Poul E, Blanpain C. 2001. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. Journal of Biological Chemistry, 276, 34631–34636.
Ladd A, Tsong Y Y, Lok J, Thau R B. 1990. Active immunization against LHRH: I. Effects of conjugation site and dose. American Journal of Reproductive Immunology, 22, 56–63.
Lee J H, Miele M E, Hicks D J, Phillips K K, Trent J M, Weissman B E, Welch D R. 1996. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. Journal of the National Cancer Institute, 88, 1731–1737.
Leenaars P P A M, Rotterdam, Koedam M A, Wester P W, Baumans V, Claassen E, Hendriksen C F M. 1998. Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice. Laboratory Animals, 32, 387–406.
Lents M P, Barbosa L P, Santana A L A, Pinheiro E E G, Mugabe L C, Biscarde C E A, Kiya C K, Machado W M, Souza R S. 2018. Immunocastration of goats using anti-gonadotrophin releasing hormone vaccine. Theriogenology, 114, 7–13.
Levy J K, Miller L A, Crawford P C, Ritchey J W, Ross M K, Fagerstone K A. 2004. GnRH immunocontraception of male cats. Theriogenology, 62, 1116–1130.
Maryam M. 2013. Production and evaluation the experimental immunocastration vaccine produced in Shiraz Razi Vaccine and Serum Research Institute, in sheep. Razi Vaccine and Serum Research Institute (RVSRI).
Meléndez D M, Marti S, Pajor E A, Moya D, Gellatly D, Janzen E D, Schwartzkopf-Genswein K S. 2017. Effect of timing of subcutaneous meloxicam administration on indicators of pain after knife castration of weaned calves. Journal of Animal Science, 95, 5218–5229.
Mellor D G, Molony V, Robertson I S. 1991. Effects of castration on behaviour and plasma cortisol concentrations in young lambs, kids and calves. Research in Veterinary Science, 51, 149–154.
Miller L A, Gionfriddo J P, Fagerstone K A, Rhyan J C, Killian G J. 2008. The single-shot GnRH immunocontraceptive vaccine (GonaCon™) in white-tailed deer: Comparison of several GnRH preparations. American Journal of Reproductive Immunology, 60, 214–223.
Molony V, Kent J E. 1997. Assessment of acute pain in farm animals using behavioral and physiological measurements. Journal of Animal Science, 75, 266–272.
Molony V, Kent J E, Robertson I S. 1995. Assessment of acute and chronic pain after different methods of castration of calves. Applied Animal Behaviour Science, 46, 33–48.
Morton D B. 2007. Vaccines and animal welfare. Revue Scientifique et Technique-Office International des Epizooties, 26, 157–163.
Moudgal N R, Jeyakumar M, Krishnamurthy H N, Sridhar S, Krihsnamurthy H, Martin F. 1997. Development of male contraceptive vaccine - a perspective. Human Reproduction Update, 3, 335–346.
Musa A, Needham T, Kotrba R, Ny V, Ceacero F. 2020. Influence of immunocastration on the temperament and habituation of common eland to routine handling. In: 46th Conference of Czech and Slovak Ethological Society Bratislava. 7–10 November, 2019, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia.
Nautrup B P, Vlaenderen I, Van Aldaz A, Mah C K. 2018. The effect of immunization against gonadotropin-releasing factor on growth performance, carcass characteristics and boar taint relevant to pig producers and the pork packing industry: A meta-analysis. Research in Veterinary Science, 119, 182–195.
Needham T, Hoffman L, Lambrechts H. 2017. Castration of male livestock and the potential of immunocastration to improve animal welfare and production traits: Invited review. South African Journal of Animal Science, 47, 731–742.
Needham T, Hoffman L, Lambrechts H. 2019. Application of immunocastration in a commercial Dohne Merino ram flock before weaning. South African Journal of Animal Science, 48, 1115–1120.
Needham T, Lambrechts H, Hoffman L. 2016. The influence of vaccination interval on growth, carcass traits and testicle parameters of immunocastrated ram lambs. Small Ruminant Research, 145, 53–57.
Oatley J, Tibary A, De Avila D, Wheaton J, McLean D, Reeves J. 2005. Changes in spermatogenesis and endocrine function in the ram testis due to irradiation and active immunization against luteinizing hormone-releasing hormone. Journal of Animal Science, 83, 604–612.
Oliveira E, Moura M, de Sá M J, Junior V, Kastelic J, Douglas R, Junior A. 2012. Permanent contraception of dogs induced with intratesticular injection of a zinc gluconate-based solution. Theriogenology, 77, 1056–1063.
Parthasarathy V, Price E O, Orihuela A, Dally M R, Adams T. 2002. Passive immunization of rams (Ovis aries) against GnRH: effects on antibody titer, serum concentrations of testosterone, and sexual behavior. Animal Reproduction Science, 71, 203–215.
Prunier A, Bonneau M, von Borell E H, Cinotti S, Gunn M, Fredriksen B, Giersing M, Morton D B, Tuyttens F A M, Velarde A. 2006. A review of the welfare consequences of surgical castration in piglets and evaluation of non-surgical methods. Animal Welfare, 15, 277–289.
Quaresma M, Antunes I C, Ribeiro M F, Prazeres S, Bessa R, Martins D. 2019. Immunocastration as an alternative to caponization: Evaluation of its effect on body and bone development and on meat color and composition. Poultry Science, 98, 2699.
Robertson I, Kent J, Molony V. 1994. Effect of different methods of castration on behaviour and plasma cortisol in calves of three ages. Research in Veterinary Science, 56, 8–17.
Sad S, Gupta H, Talwar G, Raghupathy R. 1991. Carrier-induced suppression of the antibody response to a ‘self’ hapten. Immunology, 74, 223.
Schanbacher B. 1982. Responses of ram lambs to active immunization against testosterone and luteinizing hormone-releasing hormone. American Journal of Physiology-Endocrinology and Metabolism, 242, E201–E205.
Schanbacher B. 1985. Effects of active immunization of the ram and bull against luteinizing hormone. Theriogenology, 24, 59–71.
Stafford K, Mellor D. 2005. The welfare significance of the castration of cattle: A review. New Zealand Veterinary Journal, 53, 271–278.
Steiner A, Janett F. 2013. Castration in the bull calf and ram lamb. Schweizer Archiv für Tierheilkunde, 155, 603–611.
Tesema B, Zhao J, Jiang X, Liu G Q, Han Y G, Wassie T. 2017. Kisspeptin recombinant oral vaccine: A master gene vaccine inhibiting the reproductive physiology and behavior of ram lambs. Vaccine, 37, 4630–4636.
Theubet G, Thun R, Hilbe M, Janett F. 2010. Effect of vaccination against GnRH (Bopriva®) in the male pubertal calf. Schweizer Archiv für Tierheilkunde, 152, 459–469.
Turkstra J, Van Der Staay F, Stockhofe-Zurwieden N, Woelders H, Meloen R, Schuurman T. 2011. Pharmacological and toxicological assessment of a potential GnRH vaccine in young-adult male pigs. Vaccine, 29, 3791–3801.
Uenoyama Y, Nakamura S, Hayakawa Y, Ikegami K, Watanabe Y, Deura C, Inoue N. 2015. Lack of pulse and surge modes and glutamatergic stimulation of luteinising hormone release in KISS1 knockout rats. Journal of Neuroendocrinology, 27, 187–197.
Ülker H, Gökdal Ö, Aygün T, Karaku F, DeAvila D M, Reeves J J. 2003. Feedlot performance and carcass characteristics of ram lambs immunized against recombinant LHRH fusion proteins at 10 weeks of age. Small Ruminant Research, 50, 213–218.
Ülker H, Yılmaz A, Karakuş F, Yörük M, Budağ C, DeAvila D, Reeves J. 2009. LHRH fusion protein immunization alters testicular development, ultrasonographic and histological appearance of ram testis. Reproduction in Domestic Animals, 44, 593–599.
Walker M P, Thompson D L, Godke R A, Honey P G. 1984. Active immunization of prepubertal bulls against testosterone: Seminal and testicular characteristics after puberty. Theriogenology, 22, 269–278.
Wassie T, Liu G, Jiang X, Tesema B, Han Y, Zhao J, Girmay S, Ahmad H. 2018. Immunization against Kisspeptin-54 perturb hypothalamic-pituitary-testicular signaling pathway in ram lambs. Theriogenology, 125, 193–202.
Wassie T, Zeng F, Jiang X, Liu G, Girmay S, Zhang M, Liu C, Bo D, Ahmed S. 2019. Recombinant B2L and Kisspeptin-54 DNA vaccine induces immunity against Orf virus and inhibits spermatogenesis in rats. Scientific Reports, 9, 16262.
Wassie T, Zeng F, Jiang X, Liu G, Kasimu H, Ling S, Girmay S. 2020. Effect of Kisspeptin-54 immunization on performance, carcass characteristics, meat quality and safety of Yiling goats. Meat Science, 166, 108139.
Wicks N, Crouch S, Pearl C A. 2013. Effects of Improvac and Bopriva on the testicular function of boars ten weeks after immunization. Animal Reproduction Science, 142, 149–159.
Windsor P, Lomax S, White P. 2016. Progress in pain management to improve small ruminant farm welfare. Small Ruminant Research, 142, 55–57.
Young C, Chang S, Seung Y, Joong B. 2003. The development an immunocastration method using tandem repeated gnrh peptide coupled to goat rotavirus VP6 protein. Proceedings of the Korean Society of Experimental Animal Sciences Conference, 58, 89–104.