Active immunization with follicle-stimulating hormone for fertility control: a 4½-year study in male rhesus monkeys

Srinath, Banavar R.; Wickings, E. Jean; Witting, Ch.; Nieschlag, Eberhard

doi:10.1016/s0015-0282(16)47187-6

Cited by 65 publications

(24 citation statements)

References 10 publications

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“…For example, administration of FSH to either GnRH antagonist-treated (23) or normal (24) macaques fully maintained spermatogonial numbers with a considerable increase in spermatocytes and spermatids. Other studies in monkeys showed that active or passive immunization against FSH results in pronounced reduction in testis size and sperm counts (25,26). In a study in hypophysectomized monkeys it was demonstrated that T alone maintains complete spermatogenesis; however, spermatogonial proliferation was impaired in the absence of FSH (27).…”

Section: Discussionmentioning

confidence: 99%

Variability in Sperm Suppression during Testosterone Administration to Adult Monkeys Is Related to Follicle Stimulating Hormone Suppression and Not to Intratesticular Androgens

Narula

O’Donnell³

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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Sex steroid-based male contraceptive regimens do not induce consistent azoospermia. The reason for this variable response is obscure. We used normal adult male monkeys, Macaca fascicularis (n ‫؍‬ 9) as a model of testosterone (T)-induced gonadotropin suppression to understand the basis for variability in spermatogenic suppression during hormonal contraception. As observed in men, T administration to these monkeys induced azoospermia in some animals and variable degrees of spermatogenic suppression in others. Based on their sperm counts, we divided these animals into two groups: azoospermic (azoo; n ‫؍‬ 4) and nonazoospermic (nonazoo; n ‫؍‬ 5) groups. Sperm density, testis volumes, and serum T, bioassayable LH (bioLH), immunoassayable FSH (immunoFSH), bioassayable FSH (bioFSH), and inhibin B were examined every 2 wk during the control period, 20 wk of T administration using SILASTIC brand (Dow Corning Corp.) implants, and recovery. Testes were biopsied for estimation of intratesticular T, dihydrotestosterone, and 5␣-androstane-3␣,17␤-diol. Serum T levels increased 1.5-to 2-fold, leading to decreased bioLH levels (48% of control) and intratesticular T levels (15% of control); neither LH nor intratesticular T levels differed between the azoo and nonazoo groups. In contrast, serum levels of FSH, by both bio-and immunoassay, during T administration were significantly lower in the azoo than in the nonazoo group. These results suggest that the degree of suppression of spermatogenesis is closely related to the degree of suppression of FSH levels and not to the levels of intratesticular androgens or to serum LH. These results imply that FSH plays a key role in supporting spermatogenesis in monkeys in this experimental regimen and suggest that maximal suppression of FSH may be essential to ensure consistent azoospermia in men during hormonal contraception. (J Clin Endocrinol Metab 87: 3399 -3406, 2002) A DMINISTRATION OF exogenous testosterone (T), either alone or in combination with other agents, produces profound suppression of spermatogenesis by inhibition of pituitary gonadotropins and depletion of testosterone within the testis (1-5). This approach is currently being investigated as a method of hormonal contraception for men. A consistent problem associated with T-based contraceptive regimens is that azoospermia is achieved in 40 -90% of men, but a varying degree of spermatogenic suppression is seen within and between various ethnic groups (6, 7). The reason for this variation remains unknown, but it is a critical question in designing and developing future hormonal contraceptives for men.A possible mechanism for such variation could be differences in residual testicular steroidogenesis (8); it remains controversial whether FSH levels in blood are important (5, 9) or not (10, 11) in the maintenance of sperm production in some men. There is a lack of evidence about the potential role of intratesticular androgens in the maintenance of spermatogenesis during hormonal contraceptive regimens. Also, there are very limited ...

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Section: Discussionmentioning

confidence: 99%

Variability in Sperm Suppression during Testosterone Administration to Adult Monkeys Is Related to Follicle Stimulating Hormone Suppression and Not to Intratesticular Androgens

Narula

O’Donnell³

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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“…Wickings & Neischlag (1980) and Raj et al (1980) confirmed this observation by showing that immunization of monkeys with oFSH disrupts spermatogenesis and results in oligospermia without causing changes in serum testosterone concen¬ tration; however, no fertility tests were conducted by either of these investigators. Srinath et al (1983) suggested that continuous active immunization of rhesus monkeys with oFSH (for more than 3 years) resulted in the monkeys starting to produce increased numbers of spermatozoa in less than 20% of the ejaculates suggesting that the animals may eventually be able to override the effect of FSH immunization. However, as only a few monkeys were used in this study and rhesus monkeys are seasonal breeders (Sehgal et al, 1986), it is not clear whether the increment in the immunized monkey seminal sperm counts reported at about the time of seasonal recrudescence (July-August) is due to factors other than FSH regulating continuous production of spermatozoa.…”

Section: Introductionmentioning

confidence: 99%

Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkeys (Macaca radiata)

Moudgal

Ravindranath²,

Murthy³

et al. 1992

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injections, nine of ten animals regained fertility, but the time taken for this depended upon the rate of decline of antibody titres. Re-boosting these monkeys with 100 \ g=m\ g oFSH after confirming that recovery had occurred revealed prompt increases in antibody titres followed once again by onset of oligo-azoospermia and infertility, underscoring the specificity of immunization effect. The immunized monkeys, apart from being acutely oligospermic, ejaculated spermatozoa that were markedly deficient in key acrosomal enzymes, such as acrosin and hyaluronidase, and motility as well as in their ability to penetrate a gel in vitro, suggesting that the infertility observed was due to gross reductions in the numbers of spermatozoa that could effectively interact with the oocyte and cause successful fertilization.

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“…The sperm morphology, motility and their ability to penetrate zona-free hamster eggs was normal. 45 In another study, active immunization of male bonnet monkeys with oFSH led to a significant decrease in the sperm count in the semen ejaculate, within 150 d post-immunization. 46 Immunization with oFSH had no significant effect on testosterone levels and animals had normal libido.…”

Section: Veterinary Applications Of Gnrh-based Contraceptive Vaccinementioning

confidence: 96%

“…44 Active immunization of male rhesus monkeys with ovine FSH (oFSH) led to decrease in spermatogenesis, without any adverse effect on the serum testosterone levels. 45 However, after two years, in spite of high anti-FSH antibody titers, immunized animals showed return of spermatogenesis with sperm count in the normal range. The sperm morphology, motility and their ability to penetrate zona-free hamster eggs was normal.…”

Section: Veterinary Applications Of Gnrh-based Contraceptive Vaccinementioning

confidence: 97%

Milestones in contraceptive vaccines development and hurdles in their application

Gupta

Shrestha

Minhas

2013

Human Vaccines & Immunotherapeutics

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Active immunization with follicle-stimulating hormone for fertility control: a 4½-year study in male rhesus monkeys

Cited by 65 publications

References 10 publications

Variability in Sperm Suppression during Testosterone Administration to Adult Monkeys Is Related to Follicle Stimulating Hormone Suppression and Not to Intratesticular Androgens

Variability in Sperm Suppression during Testosterone Administration to Adult Monkeys Is Related to Follicle Stimulating Hormone Suppression and Not to Intratesticular Androgens

Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkeys (Macaca radiata)

Milestones in contraceptive vaccines development and hurdles in their application

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