A practicable immunological approach to block spermatogenesis without loss of androgens.

Abstract

The intrinsic capacity of the immune system to elicit immune response selectively against late developing sperm proteins has been mobilized to intercept spermatogenesis. Bacillus Calmette-Guerin given in appropriate doses intratesticularly is effective in bringing about this effect. In dogs and rhesus monkeys, the sperm count in the semen declined precipitously, and almost complete azospermia was attained in 4-6 weeks after immunization. The few sperm cells that were present were immotile. Examination of serial sections of testes in immunized rats showed about 98% of the tubules to be devoid of sperm. The tubules were partially or fully atrophied. The basement membrane was, however, intact and the peritubular cell layer was normal. Sertoli cell nuclei were apparently normal but the cytoplasm was vacuolated and, in most cells, partially disintegrated. The lumen of the tubules was exhausted of formed elements and at times filled with eosinophilic debris. Leydig cells were present and hyperplasia of interstitial cells was seen, with massive infiltration of leukocytes. Blood testosterone levels were in the normal range and Leydig cells were responsive to gonadotropins. Libido was intact. The method was applicable to a variety of mammalian species. The implications of the results are discussed.Numerous attempts are being made to develop new methods for control of male fertility. Progestogens have been used to suppress the production and, possibly, the maturation of sperm cells (1-4). Dosages required to achieve azospermia, however, appear to vary widely from individual to individual; pregnancies have been recorded in couples in whom the male partner was seemingly on high dose, which, however, produced in him only oligospermia and not azospermia (4). Intake of these steroids is accompanied by undesirable side effects, such as loss of libido (4, 5), presumably by virtue of their antiandrogenic action (6), thus demanding the supplementation of the regime with androgens (7).As an alternative to steroidal contraception, the feasibility of immunization against a number of sperm antigens is being explored. The most promising of the sperm-specific antigens are LDH-x (8) and acrosin (9). A major limitation in their practical use is the difficulty in producing potent immune response in iso-or heterospecies; in spite of recourse to strong adjuvants such as Freund's complete adjuvant, a reduction, but not complete block, of fertility is obtained in test animals (10).This communication describes a simple and effective procedure for achieving aspermatogenesis in mammals. The method is based on the rationale that the body's immune system is tolerant to only those testicular constituents that are made and functional during fetal life. New proteins emerging with the onset of spermatogenesis in postnatal years are "foreign" to the immune system and intrinsically elicit immune response if the opportunity is given to do so. The validity of this hypothesis is supported by the frequent formation of antisperm antibodies in subject...

Immunological sterilization of male dogs by BCG

“…4p). This mode of immunization does not cause a fall in the blood androgen levels as reported elsewhere (Talwar et al 1979). (2) At high doses (75-1 10 units), Fig.…”

“…It further reports the effective use of an attenuated mycobacterium BCG, which has been in clinical use for decades, for immuiiological sterilization of dogs with no serious side effects. The rationale, wide applicability and benefits of BCG as an agent to achieve aspermatogenesis in mammals have been discussed elsewhere (Talwar et al 1979).…”

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

“…Immunogens that can be used in males are currently restricted to follicle-stimulating (FSH), luteinizing (LH) and gonadotrophin-releasing (GnRH) hormones, although immunization with nonspecific proteins has also been suggested (Talwar et al, 1979). The choice of oFSH as an immunogen was based on the results of an earlier study in which we showed that chronic passive immunoneutralization of endogenous FSH of adult male monkeys with characterized antiserum to oFSH leads to a drastic reduction in number of spermatozoa and onset of infertility (Murty et ai, 1979a;Sheela Rani et ai, 1978), but the fertility of these monkeys could be restored by stopping antiserum injections.…”

Immunological Control of Male Fertility

“…Leydig cells are however present intact histologically and are functional. Blood testosterone levels are undiminished [34]. Administration of gonadotropins such as hCG evokes a normal response with rise in blood testosterone levels (Fig.…”

“…A critically important component in the FCA is the mycobacteria 1241. Use was made of an attenuated mycobacterium-Bacillus Calmette Guerin (BCG) [34]. BCG has been of considerable value in immunoprophylaxis against tuberculosis and in immunotherapy of some cancers [16].…”