The epididymal immune balance: a key to preserving male fertility / 亚洲男科学杂志(英文版)

Up to 15% of male infertility has an immunological origin, either due to repetitive infections or to autoimmune responses mainly affecting the epididymis, prostate, and testis. Clinical observations and epidemiological data clearly contradict the idea that the testis confers immune protection to the whole male genital tract. As a consequence, the epididymis, in which posttesticular spermatozoa mature and are stored, has raised some interest in recent years when it comes to its immune mechanisms. Indeed, sperm cells are produced at puberty, long after the establishment of self-tolerance, and they possess unique surface proteins that cannot be recognized as self. These are potential targets of the immune system, with the risk of inducing autoantibodies and consequently male infertility. Epididymal immunity is based on a finely tuned equilibrium between efficient immune responses to pathogens and strong tolerance to sperm cells. These processes rely on incompletely described molecules and cell types. This review compiles recent studies focusing on the immune cell types populating the epididymis, and proposes hypothetical models of the organization of epididymal immunity with a special emphasis on the immune response, while also discussing important aspects of the epididymal immune regulation such as tolerance and tumour control.

Evaluation of different methods of sperm immunization in mice

Antifertility effects of naturally occuring antisperm antibody [ASA] in infertile couples and studies on experimental immunization of various animals with sperm antigens represent ASA as an immunocontraceptive target. The effects of different factors on sperm immunogenecity and ASA production have been studied and different results have been reported. In this study, whole sperm immunization was evaluated. In this experimental study, whole mice sperm with different adjuvants i.e. complete Freund's adjuvant [CFA], incomplete Freund's adjuvant [ICFA], cholera toxin subunit- beta [CTS-beta] were administrated to mice by different routes; Intramuscular [IM], Subcutaneous [SC], Intranasal [IN], Intra peritoneal [IP], Intrarectal [IR], Intravaginal [IVA] and oral. Control groups were inoculated with phosphate buffer saline [PBS] plus corresponding adjuvant. Immunization was carried out on day 0,7,14,28 and ASA titers were detected by indirect immunofluorescence [IFA] technique. The results were compared between control and experimental groups by Mann Whitney and Fisher exact tests. The number of positive mice for ASA in IM, IN and SC experimental and control groups were significantly different [P=0.01, P=0.01, P=0.04 respectively]. However, there were no significant differences between the IR, IVA, and oral experimental and control groups. No differences were observed between ASA in vaginal washing of all groups. Due to high mortality, the IP group was excluded from the study. It can be concluded that whole sperm antigen can induce immune response in female mice by IM. SC and IN routes, but not through IAV, IR and oral administration routes

Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35

Immunocastration is a considerable alternative to a surgical castration method especially in male animal species for alleviating unwanted male behaviors and characteristics. Induction of high titer of antibody specific for gonadotropin-releasing hormone (GnRH) correlates with the regression of testes. Fusion proteins composed of canine GnRH and T helper (Th) cell epitope p35 originated from canine distemper virus (CDV) F protein and goat rotavirus VP6 protein were produced in E. coli. When these fusion proteins were injected to male dogs which were previously immunized with CDV vaccine, the fusion protein of GnRH-CDV Th cell epitope p35 induced much higher antibody than that of GnRH-rotavirus VP6 protein or GnRH alone. The degeneration of spermatogenesis was also verified in the male dogs immunized with the fusion protein of GnRH-CDV Th cell epitope p35. These results indicate that canine GnRH conjugated to CDV Th cell epitope p35 acted as a strong immunogen and the antibody to GnRH specifically neutralized GnRH in the testes. This study also implies a potential application of GnRH-based vaccines for immunocastration of male pets.

Field assessment of recombinant Schistosoma japonicum 26 kDa glutathione S-transferase in Chinese water buffaloes.

We have shown previously that anti-fecundity immunity can be induced experimentally against recombinant 26 kDa glutathione S-transferase (reSjc26GST) in Chinese water buffaloes (Bos buffelus), important reservoir hosts for Schistosoma japonicum in China. In the field study described here, we immunized buffaloes with reSjc26GST to induce protective immunity against S. japonicum and to evaluate its effectiveness in controlling schistosomiasis japonica. We selected two villages as test and control groups in inside-embankment areas endemic for schistosomiasis japonica. The buffaloes in the test village were vaccinated with reSjc26GST, whereas those in the control village were not. The indicators of the effect of the vaccine included the generation of specific IgG antibodies in the vaccinated buffaloes, changes in the prevalence and infection intensity in buffaloes and village children, changes in the density of infected snails, and changes in the infectivity of water bodies (assessed by sentinel mice) in transmission areas adjacent to both villages. Twenty months after vaccination, the infection rate of buffaloes in the test village was decreased by 60.4% (from an initial prevalence of 13.5% to 5.4%), and 67.9% when compared with that in the control village (initial prevalence of 16.7%). However, the infection rate in village children remained unchanged. The density of infected snails decreased by 71.4%, from 0.0049/0.11 m2 to 0.0014/0.11m2 in the high transmission area outside the embankment in the test village. There was no change in the infectivity of the water body transmission areas between the test and control villages. The levels of specific antibodies to reSjc26GST showed a continuous increase after vaccination. These results indicate that protective immunity was induced and maintained in buffaloes after vaccination with reSjc26GST. The vaccine could thus play a significant role in reducing S. japonicum transmission caused by water buffaloes in the Lake region of China.

Espermograma: indicaciones e interpretación

La evaluación y tratamiento integral del varón infértil es requisito indispensable para el logro de embarazos, No siempre se consigue conocer la cuasa de la infertilidad masculina. La evaluación convencional y funcional del semen según los criterios actualizados de la Organización Mundial de la Salud nos premite dar un diagnóstico y tratamiento más adecuado y científicos a la pareja infértil. Estos criterios se han constituido en la referencia estándar para todos los laboratorios que analizan muestras de semen humano. Las técnicas de reproducción asistida permiten a los hombres infértiles, en un procentaje muy alto, realizar sus deseos de paternidad biológica. En este módulo se definen las características normales y anormales del semen y se describen los diferentes procedimientos que componen un espermograma completo; además, se presentanlas indicaciones y la interpretacion de sus resultados.

Effects of immunization with sperm specific lactate dehydrogenase with & without muramyl dipeptide as adjuvant.

The effect of sperm specific lactate dehydrogenase-C4 (LDH-C4) alone or with muramyl dipeptide (MDP) and Freund's complete adjuvant (FCA) on immune responses and breeding capacity have been studied in isogeneic C57 BI/Ks (H-2d) mice. Results per se suggested that LDH-C4 generates isoantibodies even in absence of adjuvant. Though MDP could be substituted for FCA as adjuvant, amplification by MDP of the antibody levels is reduced to half that obtained with FCA. LDH-B4 from kidney did not produce any antibody response under similar conditions. Systemic immunization with LDH-C4 did not reduce the overall pregnancy rate but reduced the frequency of embryo resorption and increased litter size significantly. However, mothers with foetal non-resorption had in general, lower antibody titres than the mothers showing foetal resorptions. The popliteal lymph node (PLN) assay for local graft versus host (LGVH) reaction revealed that the maternal lymphocyte cell competence was depressed by the sperm specific isozyme during gestation; depression in stimulation index was associated with the low antibody titre group. MDP, like LDH-C4 alone did not modify LGVH reaction significantly although it exerted a similar effect as LDH-C4 in embryo protection.

Regulation of fertility in female mice after immunization with human sperm specific LDH: role in conception and contraception.

Effects on fertility of female mice after hyper-immunization with human lactate dehydrogenase-C4 have been studied at (50 + 25 x 4) and (50 + 50 x 4) micrograms doses of protein for two consecutive cycles of pregnancy. Results of heterologous immunization are described in relation to the role of LDH-C4 in conception and contraception. (i) Low dose of Immunization produced higher antibody (Ab) titer as tested before mating followed by higher infertility (70%) than by a higher dose of immunogen (46%), taking pregnancy as the end point. (ii) However, the results were reversed after second mating. For example, low dose of immunogen produced insignificant infertility, whereas high dose of immunogen gave 80% infertility. Similar order was shown by humoral Ab titer before mating i.e., high infertility was associated with high Ab titer and viceversa. (iii) It shows that the LDH-C4 induced infertility is reversible as is evidenced by low dose of immunization. (iv) In contrary to infertile dams, immunized fertile dams delivered a significantly higher litter size as compared to non-immunized control dams. It is concluded that immunity due to LDH-C4 is beneficial for embryo survival suggesting an immuno-suppressive nature of LDH-C4. Nonetheless, infertility ensues when immune-suppression is overcome by its own immune-activation.

A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat.

Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses.