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

Aponte, Pedro M.; Gutiérrez-Reinoso, Miguel A.; Sanchez-Cepeda, E. G.; García-Herreros, Manuel

doi:10.1017/s1751731117002129

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…Thus, the onset of spermatogenesis is characterized by an increase in germ cell (GCs) numbers [1–4,6], representing a gradual and complex activation of sets of differentiation genes. The study of the prepubertal period and the role of different spermatogenic factors involved is important for the prediction of future reproductive performance in adult males, with the goal of better impacting the reproductive management of farm animals [7,8].…”

Section: Introductionmentioning

confidence: 99%

Differential role of r-met-hu G-CSF on male reproductive function and development in prepubertal domestic mammals

Aponte¹,

Gutiérrez-Reinoso

Sanchez-Cepeda

et al. 2019

PLoS ONE

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The understanding of mammalian spermatogenesis niche factors active during sexual development may be leveraged to impact reproduction in farm animals. The aim of this study was to evaluate the effects of r-met-hu/G-CSF (filgrastim) on prepubertal sexual development of guinea pigs (Cavia porcellus) and ram lambs (Ovis aries). Individuals of both species were administered r-met-hu/G-CSF daily for 4 days. During and after administration protocols, testicular function and development were assessed through hematological responses, hormonal profiles (gonadotropins, testosterone and cortisol) testicular morphometry and germ cell kinetics. As expected, r-met-hu/G-CSF acutely mobilized white-lineage blood cells in both species. LH was increased by r-met-hu/G-CSF in guinea pigs (P<0.01) but T remained unchanged. In ram lambs gonadotropins and T increased in dose-response fashion (P<0.01) while cortisol values were stable and similar in treated and control animals (P>0.05). In guinea pigs there were no differences in testicular weights and volumes 2-mo after r-met-hu/G-CSF application (P>0.05). However, ram lambs showed a dose-response effect regarding testis weight (P<0.05). 66.66% of ram lambs had initial testes not yet in meiosis or starting the first spermatogenic wave. After 60-days only 25% of control animals were pubertal while all treated animals (1140-μg) had reached puberty. We propose an integrated hypothesis that G-CSF can stimulate spermatogenesis through two possible ways. 1) r-met-hu/G-CSF may go through the brain blood barrier and once there it can stimulate GnRH-neurons to release GnRH with the subsequent release of gonadotrophins. 2) a local testicular effect through stimulation of steroidogenesis that enhances spermiogenesis via testosterone production and a direct stimulation over spermatogonial stem cells self-renewal. In conclusion, this study shows that r-met-hu/G-CSF differentially affects prepubertal sexual development in hystricomorpha and ovine species, a relevant fact to consider when designing methods to hasten sexual developmental in mammalian species.

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Section: Introductionmentioning

confidence: 99%

Differential role of r-met-hu G-CSF on male reproductive function and development in prepubertal domestic mammals

Aponte¹,

Gutiérrez-Reinoso

Sanchez-Cepeda

et al. 2019

PLoS ONE

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“…Lents et al (2018) found azoospermia of 83.33% in goats immunocastrated with 1.0 and 0.5 mL of Bopriva. Aponte et al (2018) evaluated the effects of active anti-GnRH immunization on the reproductive function of lambs and observed that spermatozoa were not found in 60% of the transverse sections of seminiferous tubules in the immunized group. Ferro et al (2004) also used an anti-GnRH vaccine in adult sheep, which had active spermatozoa in only 19% to 28% of the tubules in immunized animals, compared with the untreated group.…”

Section: Seminal Fluid Production and Qualitymentioning

confidence: 99%

“…Immunocastration has been proven to be effective, and several specific vaccines are available on the market for swine (Dunshea et al, 2001;Zeng et al, 2002) and bovines (Amatayakul-Chantler et al, 2013;Pérez-Linares et al, 2017). Although anti-GnRH vaccines have already been studied in ovine (Han et al, 2015;Aponte et al, 2018) and caprine species (Lents et al, 2018), there is still no specific vaccine for these species on the market, and a vaccination protocol is lacking.…”

Section: Introductionmentioning

confidence: 99%

“…Different results have been obtained for different administration protocols and vaccination strategies for immunocastration in sheep (Needham et al, 2016;Aponte et al, 2018). Therefore, it is essential to establish an effective vaccination protocol capable of promoting an adequate response while maintaining animal performance and improving carcass characteristics and meat quality (Needham et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Reproductive parameters of lambs immunocastrated with anti-GnRH vaccine

et al. 2021

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The objective of this study was to evaluate the testicular biometric, seminal, and plasma testosterone levels in lambs subjected to an anti-GnRH vaccine as a method of castration. Thirty entire, crossbred Santa Inês male lambs were randomly distributed into three treatment (T): T1 was the control group, with the administration of 1 mL of saline solution subcutaneously (SC); 1.0 and 0.5 mL of an anti-GnRH vaccine were administered SC in T2 and T3, respectively. Testicular biometric variables, physical and morphological variables of semen, and plasma testosterone concentrations were evaluated. At D60, there was a reduction in testicular length, width, thickness, and scrotal circumference of the immunocastrated animals regardless of the vaccine dose used (P < 0.05). A reduction in semen physical variables at both dosages (P < 0.05) was observed, with azoospermia, in 80% and 70% of animals in the T2 and T3 groups, respectively. At D60, the immunocastrated animals also showed an increase in spermatozoa defects (P < 0.05), whereas plasma testosterone concentration decreased (P < 0.05). Immunocastration of lambs using the Bopriva vaccine at doses of 1.0 and 0.5 mL is efficient in inducing azoospermia in up to 80% of animals, although two doses in a 30-day interval are necessary for it to be an effective and safe method. Efficacy was demonstrated through a reduction in serum testosterone levels, testicular biometry, and seminal fluid analysis. Considering the efficacy of both doses in this study, we recommend using the lower dose (0.5 mL), which will allow for a 50% reduction in vaccine costs.

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“…GnRH is a wellstudied target in animal immunocontraception with continuing interest. [5][6][7] Given that GnRH is a small (10 amino acids) 'self' protein, it requires conjugation to a larger carrier protein for increased antigenicity. Most of the GnRH-based vaccines are chemical conjugates of multiple GnRH copies with carrier proteins such as tetanus toxoid, 8 diphtheria toxoid, 9 keyhole limpet hemocyanin, 10 Concholepas concholepas hemocyanin (blue protein) 4 or ovalbumin.…”

Section: Introductionmentioning

confidence: 99%

Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats

Johnson

Jones

Kraneburg

et al. 2019

Journal of Feline Medicine and Surgery

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Objectives Phage–gonadotropin-releasing hormone (GnRH) constructs with potential contraceptive properties were generated in our previous study via selection from a phage display library using neutralizing GnRH antibodies as selection targets. In mice, these constructs invoked the production of antibodies against GnRH and suppressed serum testosterone. The goal of this study was to evaluate this vaccine against GnRH for its potential to suppress reproductive characteristics in cats. Methods Sexually mature male cats were injected with a phage–GnRH vaccine using the following treatment groups: (1) single phage–GnRH vaccine with adjuvant; (2) phage–GnRH vaccine without adjuvant and half-dose booster 1 month later; or (3) phage–GnRH vaccine with adjuvant and two half-dose boosters with adjuvant 3 and 6 months later. Anti-GnRH antibodies and serum testosterone, testicular volume and sperm characteristics were evaluated monthly for 7–9 months. Results All cats developed anti-GnRH antibodies following immunization. Serum antibody titers increased significantly after booster immunizations. In group 3, serum testosterone was suppressed 8 months after primary immunization. Total testicular volume decreased in group 1 by 24–42% and in group 3 by 15–36% at 7 months after immunization, indicating potential gonadal atrophy. Vacuolation of epididymides was observed histologically. Although all cats produced sperm at the conclusion of the study, normal morphology was decreased as much as 38%. Phage alone produced no local or systemic reactions. Immunization of phage with AdjuVac produced unacceptable injection site reactions. Conclusions and relevance Our phage-based vaccine against GnRH demonstrated a potential for fertility impairment in cats. Future research is required to optimize vaccine regimens and identify animal age groups most responsive to the vaccine. If permanent contraception (highly desirable in feral and shelter cats) cannot be achieved, the vaccine has a potential use in zoo animals or pets where multiple administrations are more practical and/or reversible infertility is desirable.

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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

Cited by 8 publications

References 32 publications

Differential role of r-met-hu G-CSF on male reproductive function and development in prepubertal domestic mammals

Differential role of r-met-hu G-CSF on male reproductive function and development in prepubertal domestic mammals

Reproductive parameters of lambs immunocastrated with anti-GnRH vaccine

Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats

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