Responsiveness of human male volunteers to immunization with ovine follicle stimulating hormone vaccine: results of a pilot study

Abstract

A study of 140 days duration was performed to examine if human male volunteers (n = 5) respond to ovine follicle stimulating hormone (oFSH) immunization (administered adsorbed on Alugel on days 1, 20, 40 and 70) by producing antibodies capable of both binding and neutralizing bioactivity of human FSH. The kinetics of antibody production for both the immunogen (oFSH) and the cross-reactive antigen (hFSH) were essentially similar. The volunteers responded only to the first two immunizations. The boosters given on days 40 and 70 were ineffective, probably because of the presence of substantial amounts of circulating antibody to oFSH. Of the antibodies generated to oFSH, 25-45% bound hFSH with a mean binding affinity of 0.65 x 10(9) +/- 0.53 M(-1). The binding capacities at the time of high (30-80 days of immunization) and low (>110 days) titres were 346 +/- 185 and 10.5 +/- 5.8 ng hFSH/ml respectively. During the period of high titre, free serum FSH (value in normal males 1-5 ng/ml) was not monitorable. A 50 microl aliquot of the antiserum obtained from different volunteers between days 30 and 80 and on day 140 blocked binding of (125)I-labelled hFSH to its receptor by 82 +/- 9.7 and 53 +/- 12.2% respectively. The antibody produced was specific for FSH, and no significant change in the values of related glycoprotein hormones (luteinizing hormone/testosterone and thyroid stimulating hormone/thyroxine) were recorded. Seminal plasma transferrin, a marker of Sertoli cell as well as of seminiferous tubular function, showed marked reduction (30-90%) following immunization with oFSH. Considering that endogenous FSH remained neutralized for approximately one sperm cycle only (65 days), the reduction in sperm counts (30-74%) exhibited by some volunteers is encouraging. Immunization with oFSH did not result in any significant changes in haematology, serum biochemistry or hormonal profiles. There was no production of antibodies capable of interacting with non-specific tissues. It is concluded that it should be possible to obtain a sustained long-term blockade of endogenous FSH action in men by using oFSH as an immunogen. This is a prerequisite for obtaining significant reduction in the quality and quantity of spermatozoa produced, thus leading to infertility.

A short evolutionary history of FSH-stimulated spermatogenesis

“…37 While there are studies showing that immunization of monkeys for FSH or FSHR brings about azoospermia, 38,39 the bulk of evidence shows that the FSH dependence of monkey spermatogenesis is very similar to that of other mammalian species, i.e. FSH is not essential, although it synergizes with T to maximize sperm output.…”

Association of Body Mass Index with Semen Quality and Sexual Hormone Levels among Men in Intrauterine Insemination

“…Normal function of the gondotrophic axis, especially normal FSH secretion, plays crucial roles in spermatogenesis [20] [21]. Several experimental and clinical studies have demonstrated the importance of FSH in regulating a normal quantitative spermatogenic process in animals and humans [22] [23]. It has also been suggested that high serum FSH levels is intimately related to a decrease of spermatogenesis function.…”

Violation of spermatogenesis and outcomesof assisted reproductive technologies in various forms of hypogonadism

“…Блокада рецепторов к ФСГ у взрос-лых макак-резусов приводит к бесплодию. Био-нейтрализация циркулирующего человеческого ФСГ снижает качество и количество сперматозо-идов [10].…”