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Active immunization against GnRH in pre-pubertal domestic mammals: testicular morphometry, histopathology and endocrine responses in rabbits, guinea pigs and ram lambs

Published online by Cambridge University Press:  24 August 2017

P. M. Aponte ,
M. A. Gutierrez-Reinoso ,
E. G. Sanchez-Cepeda  and
M. Garcia-Herreros
P. M. Aponte*
Affiliation:
Colegio de Ciencias Biológicas y Ambientales, Universidad San Francisco de Quito (USFQ), Campus Cumbayá, Diego de Robles y Vía Interoceánica, 170157 Quito, Ecuador Colegio de Ciencias de la Salud, Escuela de Medicina Veterinaria, Universidad San Francisco de Quito (USFQ), Campus Cumbayá, Diego de Robles y Vía Interoceánica, 170157 Quito, Ecuador
M. A. Gutierrez-Reinoso
Affiliation:
Faculty of Veterinary Medicine, Technical University of Cotopaxi (UTC), 0501491 Latacunga, Ecuador
E. G. Sanchez-Cepeda
Affiliation:
AGROCALIDAD, 180103, Ambato, Ecuador
M. Garcia-Herreros*
Affiliation:
National Secretariat of Higher Education, Science, Technology and Innovation (SENESCYT), 170516Quito, Ecuador Instituto Nacional de Investigação Agrária e Veterinária, I. P. (INIAV, I.P.), Polo de Santarém, Quinta da Fonte Boa, 2005-048, Santarém, Portugal
*
†E-mail: [email protected]; [email protected]
†E-mail: [email protected]; [email protected]
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Abstract

Effective tools for male contraception are important in the control of reproduction in animal populations. The aim of the present study was to evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on male reproductive function assessing testicular morphological changes and serum-gonadotropin levels in pre-pubertal rabbits, guinea pigs and ram lambs. An anti-GnRH vaccine was developed by linking a GnRH-homologous molecule to a tetanus clostridial toxoid (Al(OH)3 coadjuvant). After vaccination protocols testicular morphometry, histopathological alterations and endocrine responses (FSH, LH, testosterone and cortisol serum levels) were evaluated. Testicular volume was significantly reduced in vaccinated animals with respect to the control group in rabbits, guinea pigs and ram lambs (P<0.05 to P<0.001). The anti-GnRH vaccine generated a reduction in testicular volume of 15-, 27- and 11-fold, respectively. Tubule diameters decreased in the vaccinated group with respect to the control ~2.0-, 1.2- and 3.5-fold, respectively (P<0.001). Tubule, intertubular and lumen volumes significantly decreased in vaccinated rabbits (P<0.05), guinea pigs and ram lambs (P<0.01). Vaccinated animals of the three species showed significant reductions in spermatogonial numbers (10- to 40-fold; P<0.01). Sperm was absent in all seminiferous tubules of all rabbits, and most individuals of guinea pigs (80%) and ram lambs (60%). No significant differences were observed between vaccinated and control groups regarding FSH and LH during the experiments in the three experimental species/models used. Testosterone, however, was only significantly lower (~22-fold, P<0.01) in vaccinated rabbits. In conclusion, the present study demonstrated that pre-pubertal active immunization against GnRH leads to endocrine disruption and marked differences on testicular morphometry, development and activity among lagomorphs, hystricomorphs and ovine species with species-specific sensitivity regarding the anti-GnRH immune response.

Keywords

GnRHvaccinesrabbitsguinea pigsram lambs
Type
Research Article
Information
animal , Volume 12 , Issue 4 , April 2018 , pp. 784 - 793
Copyright
© The Animal Consortium 2017 

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References

Adams, TE, Daley, CA, Adams, BM and Sakurai, H 1996. Testes function and feedlot performance of bulls actively immunized against gonadotropin-releasing hormone: effect of age at immunization. Journal of Animal Science 74, 950–954.Google Scholar
Anjum, S, Krishna, A, Sridaran, R and Tsutsui, K 2012. Localization of gonadotropin-releasing hormone (GnRH), gonadotropin-inhibitory hormone (GnIH), kisspeptin and GnRH receptor and their possible roles in testicular activities from birth to senescence in mice. Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology 317, 630–644.Google Scholar
Aponte, PM 2015. Spermatogonial stem cells: current biotechnological advances in reproduction and regenerative medicine. World Journal of Stem Cells 7, 669–680.Google Scholar
Auclair, D, Sowerbutts, SF and Setchell, BP 1995. Effect of active immunization against testosterone on plasma gonadotrophin concentrations, spermatogenic function, testicular blood flow, epididymis mass and mating behaviour in adult rams. Journal of Reproduction and Fertility 104, 17–26.Google Scholar
Bahk, JY, Hyun, JS, Chung, SH, Lee, H, Kim, MO, Lee, BH and Choi, WS 1995. Stage specific identification of the expression of GnRH mRNA and localization of the GnRH receptor in mature rat and adult human testis. The Journal of Urology 154, 1958–1961.Google Scholar
Bilaspuri, GS and Guraya, SS 1986. The seminiferous epithelial cycle and spermatogenesis in rams (Ovis aries). Theriogenology 25, 485–505.Google Scholar
Boukenaoui, N, Moudilou, E, Chevalier, C, Amirat, Z, Exbrayat, J-M and Khammar, F 2012. Postnatal changes in testicular development and androgen receptors immunolocalization in D’Man ram lambs. Folia Histochemica Et Cytobiologica 50, 38–45.CrossRefGoogle ScholarPubMed
Ciaramella, V, Chianese, R, Pariante, P, Fasano, S, Pierantoni, R and Meccariello, R 2015. Expression analysis of Gnrh1 and Gnrhr1 in spermatogenic cells of rat. International Journal of Endocrinology 2015, 1–8.Google Scholar
Clarke, IJ and Pompolo, S 2005. Synthesis and secretion of GnRH. Animal Reproduction Science 88, 29–55.Google Scholar
Clayton, RN 1985. Role of GnRH in the maturation of pituitary gonadotroph function. Journal of Reproduction and Fertility 75, 307–315.Google Scholar
Clermont, Y 1960. Cycle of the seminiferous epithelium of the guinea pig. A method for identification of the stages. Fertility and Sterility 11, 563–573.Google Scholar
Goubau, S, Silversides, DW, Gonzalez, A, Laarveld, B, Mapletoft, RJ and Murphy, BD 1989. Immunization of cattle against modified peptides of gonadotropin releasing hormone conjugated to carriers: effectiveness of Freund’s and alternative adjuvants. Theriogenology 32, 557–567.Google Scholar
Han, XF, Cheng, W, Chen, ZY, Du, XG, Cao, XH and Zeng, XY 2014. Initiation of active immunization against testosterone during early puberty alters negative feedback regulation of the hypothalamic-pituitary-testicular axis in rabbits. Domestic Animal Endocrinology 48, 126–135.Google Scholar
Hernandez-Medrano, JH, Williams, RW, Peters, AR, Hannant, D, Campbell, BK and Webb, R 2012. Neonatal immunisation against a novel gonadotrophin-releasing hormone construct delays the onset of gonadal growth and puberty in bull calves. Reproduction, Fertility, and Development 24, 973–982.CrossRefGoogle ScholarPubMed
Holt, WV 1977. Postnatal development of the testes in the cuis, Galea Musteloides. Laboratory Animals 11, 87–91.Google Scholar
Howard, CV and Reed, MG 1998. Number estimation. In Unbiased stereology. Three-dimensional measurement in microscopy (ed. CV Howard and MG Reed), pp. 69–106. Bios Scientific Publishers Limited, Oxford, UK.Google Scholar
Ison, SH, Clutton, RE, Di Giminiani, P and Rutherford, KMD 2016. A review of pain assessment in pigs. Frontiers in Veterinary Science 3, 1–16.Google Scholar
Jago, JG, Bass, JJ and Matthews, LR 1997. Evaluation of a vaccine to control bull behaviour. Proceedings of the New Zealand Society of Animal Production 57, 91–95.Google Scholar
Janett, F, Gerig, T, Tschuor, AC, Amatayakul-Chantler, S, Walker, J, Howard, R, Piechotta, M, Bollwein, H, Hartnack, S and Thun, R 2012. Effect of vaccination against gonadotropin-releasing factor (GnRF) with Bopriva® in the prepubertal bull calf. Animal Reproduction Science 131, 72–80.Google Scholar
Janett, F, Stump, R, Burger, D and Thun, R 2009. Suppression of testicular function and sexual behavior by vaccination against GnRH (Equity) in the adult stallion. Animal Reproduction Science 115, 88–102.Google Scholar
Jimenez-Liñan, M, Rubin, BS and King, JC 1997. Examination of guinea pig luteinizing hormone-releasing hormone gene reveals a unique decapeptide and existence of two transcripts in the brain. Endocrinology 138, 4123–4130.Google Scholar
Kauffold, J, Rohrmann, H, Boehm, J and Wehrend, A 2010. Effects of long-term treatment with the GnrH agonist deslorelin (Suprelorin) on sexual function in boars. Theriogenology 74, 733–740.Google Scholar
Kutzler, M and Wood, A 2006. Non-surgical methods of contraception and sterilization. Theriogenology 66, 514–525.Google Scholar
Martí, JI, Aparicio, IM and García-Herreros, M 2011. Head morphometric changes in cryopreserved ram spermatozoa are related to sexual maturity. Theriogenology 75, 473–481.Google Scholar
Marti, S, Devant, M, Amatayakul-Chantler, S, Jackson, JA, Lopez, E, Janzen, ED and Schwartzkopf-Genswein, KS 2015. Effect of anti-gonadotropin-releasing factor vaccine and band castration on indicators of welfare in beef cattle. Journal of Animal Science 93, 1581–1591.Google Scholar
Miesner, MD and Anderson, DE 2015. Surgical management of common disorders of feedlot calves. The Veterinary Clinics of North America: Food Animal Practice 31, 407–424. vi–vii.Google Scholar
Miller, LA, Johns, BE and Killian, GJ 2000. Immunocontraception of white-tailed deer with GnRH vaccine. American Journal of Reproductive Immunology 44, 266–274.Google Scholar
Morton, D 1988. The use of rabbits in male reproductive toxicology. Environmental Health Perspectives 77, 5–9.Google Scholar
Niewiesk, S 2014. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Frontiers in Immunology 5, 1–15.Google Scholar
Occhio, MJD’, Aspden, WJ and Trigg, TE 2001. Sustained testicular atrophy in bulls actively immunized against GnRH: potential to control carcase characteristics. Animal Reproduction Science 66, 47–58.Google Scholar
Rodríguez, RE and Wettstein, RM 2004. Quantitative study on guinea pig spermatogenesis shows a relative high percentage of early meiotic prophase stages. The Anatomical Record 278, 493–504.Google Scholar
Simoni, M, Weinbauer, GF, Gromoll, J and Nieschlag, E 1999. Role of FSH in male gonadal function. Annales D’endocrinologie 60, 102–106.Google Scholar
Swierstra, EE and Foote, RH 1963. Cytology and kinetics of spermatogenesis in the rabbit. Journal of Reproduction and Fertility 5, 309–322.Google Scholar
Tanaka, T, Kanatsu-Shinohara, M, Lei, Z, Rao, CV and Shinohara, T 2016. The luteinizing hormone-testosterone pathway regulates mouse spermatogonial stem cell self-renewal by suppressing WNT5A expression in sertoli cells. Stem Cell Reports 7, 279–291.Google Scholar
Yasser, A, Mahmoud, MA-E and Gamal, KMA 2012. Histological and histomorphometric changes of the rabbit testis during postnatal development. Research Journal of Veterinary Sciences 5, 42–50.Google Scholar
Yeh, S, Tsai, M-Y, Xu, Q, Mu, X-M, Lardy, H, Huan, K-E, Lin, H, Yeh, S-D, Altuwaijri, S, Zhou, X, Xing, L, Boyce, BF, Hung, M-C, Zhang, S, Gan, L, Chang, C and Hung, M-C 2002. Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proceedings of the National Academy of Sciences of the United States of America 99, 13498–13503.Google Scholar