Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2019 ; Vol.29-4: 658~664

AuthorYong-Hyun Kim, Byung-Joo Park, Hee-Seop Ahn, Sang-Hoon Han, Hyeon-Jeong Go, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, Sang-Won Lee, In-Soo Choi
Place of dutyDepartment of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Republic of Korea
TitleImmunocontraceptive Effects in Male Rats Vaccinated with Gonadotropin-Releasing Hormone-I and -II Protein Complex
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-4
AbstractImmunocontraception has been suggested as an optimal alternative to surgical contraception in animal species. Many immunocontraceptive vaccines have been designed to artificially produce antibodies against gonadotropin-releasing hormone-I (GnRH-I) which remove GnRH-I from the vaccinated animals. A deficiency of GnRH-I thereafter leads to a lack of gonadotropins, resulting in immunocontraception. In this study, we initially developed three immunocontraceptive vaccines composed of GnRH-I, GnRH-II, and a GnRH-I and –II (GnRHI+ II) complex, conjugated to the external domain of Salmonella Typhimurium flagellin. As the GnRH-I+II vaccine induced significantly (p < 0.01) higher levels of anti-GnRH-I antibodies than the other two vaccines, we further evaluated its immunocontraceptive effects in male rats. Mean testis weight in rats (n = 6) inoculated twice with the GnRH-I+II vaccine at 2-week intervals was significantly (p < 0.01) lower than in negative control rats at 10 weeks of age. Among the six vaccinated rats, two were non-responders whose testes were not significantly reduced when compared to those of negative control rats. Significantly smaller testis weight (p < 0.001), higher anti-GnRH-I antibody levels (p < 0.001), and lower testosterone levels (p < 0.001) were seen in the remaining four responders compared to the negative control rats at the end of the experiments. Furthermore, seminiferous tubule atrophy and spermatogenesis arrest were found in the testis tissues of responders. Therefore, the newly developed GnRHI+ II vaccine efficiently induced immunocontraception in male rats. This vaccine can potentially also be applied for birth control in other animal species.
Full-Text
Key_wordImmunocontraception, gonadotropin-releasing hormone, antibody, testosterone, spermatogenesis
References
  1. Delves PJ. 2004. How far from a hormone-based contraceptive vaccine? J. Reprod. Immunol. 62: 69-78.
    CrossRef
  2. Desaulniers AT, Cederberg RA, Lents CA, White BR. 2017. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals. Front. Endocrinol. 8: 269.
    CrossRef
  3. Thompson Jr DL. 2000. Immunization against GnRH in male species (comparative aspects). Anim. Reprod. Sci. 60: 459-469.
    CrossRef
  4. Kirkpatrick JF, Lyda RO, Frank KM. 2011. Contraceptive vaccines for wildlife: a review. Am. J. Reprod. Immunol. 66:40-50.
    Pubmed CrossRef
  5. Levy JK. 2011. Contraceptive vaccines for the humane control of community cat populations. Am. J. Reprod. Immunol. 66:63-70.
    Pubmed CrossRef Pubmed Central
  6. Kochman K. 2012. Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor. J. Anim. Feed Sci. 21: 3-30.
    CrossRef
  7. Kauffman A. 2004. Emerging functions of gonadotropinreleasing hormone II in mammalian physiology and behaviour. J. Neuroendocrinol. 16: 794-806.
    CrossRef
  8. Khan MA, Prevost M, Waterston MM, Harvey MJ, Ferro VA. 2007. Effect of immunisation against gonadotrophin releasing hormone isoforms (mammalian GnRH-I, chicken GnRH-II and lamprey GnRH-III) on murine spermatogenesis. Vaccine 25: 2051-2063.
    CrossRef
  9. Earl ER, Waterston MM, Aughey E, Harvey MJ, Matschke C, Colston A, et al. 2006. Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs. Vaccine 24: 3172-3183.
    CrossRef
  10. Qian F, Guo A, Li M, Liu W, Pan Z, Jiang L, et al. 2015. Salmonella flagellin is a potent carrier–adjuvant for peptide conjugate to induce peptide-specific antibody response in mice. Vaccine 33: 2038-2044.
    CrossRef
  11. Hu W, Xiang J-Y, Kong P, Liu L, Xie Q, Xiang H. 2017. Expression and characterization of a single-chain variable fragment against human LOX-1 in Escherichia coli and brevibacillus choshinensis. J. Microbiol. Biotechnol. 27: 965-974.
    CrossRef
  12. Choi GS, Kim HJ, Kim EJ, Lee SJ, Lee Y, Ahn J-H. 2018. Stepwise synthesis of quercetin bisglycosides using engineered Escherichia coli. J. Microbiol. Biotechnol. 28: 1859-1864.
  13. Song Y, Kim D, Nam H, Lee J, Park S, Song C, et al. 2012. Evaluation of the efficacy of immunocastration vaccine composed of gonadotrophin-releasing hormone conjugated with Salmonella typhimurium flagellin in rats. Reprod. Domest. Anim. 47: e47-e50.
    CrossRef
  14. Kim E, Myoung J. 2018. Hepatitis E virus papain-like cysteine protease inhibits type I interferon induction by down-regulating melanoma differentiation-associated gene 5. J. Microbiol. Biotechnol. 28: 1908-1915.
  15. Kang S, Choi C, Choi I, Han K-N, Roh SW, Choi J, et al.2018. Hepatitis E virus methyltransferase inhibits type I interferon induction by targeting RIG-I. J. Microbiol. Biotechnol.28: 1554-1562.
  16. Park C, Kim Y-H, Lee S-R, Park S, Jung Y, Lee Y, et al. 2018. Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity. J. Microbiol. Biotechnol. 28: 1547-1553.
  17. Cook R, Popp J, Kastelic J, Robbins S, Harland R. 2000. The effects of active immunization against GnRH on testicular development, feedlot performance, and carcass characteristics of beef bulls. J. Anim. Sci. 78: 2778-2783.
    CrossRef
  18. Dunshea F, Colantoni C, Howard K, McCauley I, Jackson P, Long K, et al. 2001. Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance. J. Anim. Sci. 79: 2524-2535.
    CrossRef
  19. Ferro V, Khan M, McAdam D, Colston A, Aughey E, Mullen A, et al. 2004. Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)—a histological comparison in male animals. Vet. Immunol. Immunopathol. 101: 73-86.
    CrossRef
  20. Han X, Gu L, Xia C, Feng J, Cao X, Du X, et al. 2015. Effect of immunization against GnRH on hypothalamic and testicular function in rams. Theriogenology 83: 642-649.
    CrossRef
  21. Levy JK, Miller LA, Crawford PC, Ritchey JW, Ross MK, Fagerstone KA. 2004. GnRH immunocontraception of male cats. Theriogenology 62: 1116-1130.
    CrossRef
  22. Cuadros C, Lopez-Hernandez FJ, Dominguez AL, McClellandM, Lustgarten J. 2004. Flagellin fusion proteins as adjuvants or vaccines induce specific immune responses. Infect. Immun.72: 2810-2816.
    CrossRef
  23. Turley CB, Rupp RE, Johnson C, Taylor DN, Wolfson J, Tussey L, et al. 2011. Safety and immunogenicity of a recombinant M2e–flagellin influenza vaccine (STF2. 4xM2e) in healthy adults. Vaccine 29: 5145-5152.
    CrossRef
  24. Han X-F, Li J-L, Zhou Y-Q, Ren X-H, Liu G-C, Cao X-H, et al. 2016. Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis. Asian J. Androl. 18: 485-491.
    CrossRef
  25. Yao Z, Si W, Tian W, Ye J, Zhu R, Li X, et al. 2018. Effect of active immunization using a novel GnRH vaccine on reproductive function in rats. Theriogenology 111: 1-8.
    CrossRef
  26. Zeng XY, Turkstra JA, Meloen RH, Liu XY, Chen FQ, Schaaper WM, et al. 2002. Active immunization against gonadotrophin-releasing hormone in Chinese male pigs:effects of dose on antibody titer, hormone levels and sexual development. Anim. Reprod. Sci. 70: 223-233.
    CrossRef
  27. Sad S, Gupta H, Talwar G, Raghupathy R. 1991. Hyporesponsiveness to a GnRH vaccine in a non-responder mouse strain is T-cell mediated. J. Reprod. Immunol. 20: 189-194.
    CrossRef



Copyright © 2009 by the Korean Society for Microbiology and Biotechnology.
All right reserved. Mail to jmb@jmb.or.kr
Online ISSN: 1738-8872    Print ISSN: 1017-7825    Powered by INFOrang.co., Ltd