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.
Adaptive Immunity ; Animals ; Epididymis/immunology* ; Fertility/immunology* ; Genital Neoplasms, Male/immunology* ; Humans ; Immunity, Innate ; Infertility, Male/immunology* ; Male ; Spermatozoa/immunology*

The epididymal protease inhibitor (Eppin) has recently been cloned in human and mice, which is specifically expressed in the epididymis and testis. Eppin is a cystine-rich secretory protein which contains signal peptide, WAP and BPTI motifs. Eppin is involved in sperm maturation and fertilization, and in the innate immune system of human epididymis. Immunocontraception with Eppin is effective and reliable, but its safety is to be further proved. This paper summarizes the effects of Eppin of fertilization and immunity, as well as its utilization in immunocontraception.
Animals ; Contraception, Immunologic ; Epididymis ; immunology ; Fertility ; physiology ; Haplorhini ; Male ; Mice ; Proteins ; immunology ; physiology ; Spermatozoa ; physiology

Seminal vesical secretion is important for male fertility. It affects semen coagulation, sperm motility, stability of sperm chromatin and suppression of the immune activity in the female reproductive tract.
Female ; Fertility ; physiology ; Genitalia, Female ; immunology ; Humans ; Male ; Semen ; cytology ; Seminal Vesicles ; immunology ; physiology ; secretion ; Sperm Count ; Sperm Motility

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.
Amino Acid Sequence ; Animals ; Antibodies/blood ; Base Sequence ; Contraception, Immunologic/methods/*veterinary ; Distemper Virus, Canine/*immunology ; Dogs/immunology/*physiology ; Epitopes, T-Lymphocyte/*immunology ; Fertility/immunology ; Gonadotropin-Releasing Hormone/chemistry/*immunology ; Male ; Molecular Sequence Data ; Organ Size ; Recombinant Proteins/immunology ; Spermatogenesis/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Testis/immunology ; Vaccines, Contraceptive/immunology

To study whether the antibody against the testis form of the nuclear autoantigenic sperm protein (tNASP) could result in reproductive failure, we successfully cloned and expressed a 339-bp cDNA fragment of mouse tNASP (mtNASP). Using mouse as a model, recombinant mtNASP (rmtNASP) and a synthetic peptide, human tNASP(393-408) (htNASP(393-408)), were investigated for their antifertility effect. Active immunization with rmtNASP or the synthesized peptide raised high antibody titers in the immunized mice. Sperm-egg binding and fusion assay were carried out in 8-10-week-old BALB/c mice. Sperm-egg binding and in vitro fertilization of mouse oocytes were inhibited by co-incubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of varying concentrations of the antisera against rmtNASP. There was a significant antifertility effect in animals immunized with rmtNASP or the synthesized peptide. The effect on fertility in the mice immunized with the synthesized peptide was reversible. Our data indicate that active immunization with rmtNASP antigen may induce a strong antibody response that causes an inhibition of fertility.
Adult ; Animals ; Autoantibodies ; administration & dosage ; immunology ; Autoantigens ; chemistry ; immunology ; pharmacology ; Contraception, Immunologic ; Female ; Fertility ; drug effects ; immunology ; Humans ; Immune Sera ; immunology ; pharmacology ; Male ; Mice ; Nuclear Proteins ; chemistry ; immunology ; pharmacology ; Rabbits ; Recombinant Proteins ; immunology ; Sequence Analysis, Protein ; Sperm Motility ; drug effects ; immunology ; Sperm-Ovum Interactions ; immunology ; Spermatozoa ; drug effects ; immunology ; Vaccines, Contraceptive ; immunology ; pharmacology

OBJECTIVETo study the relationship between the positive antisperm antibody (AsAb) and nitric oxide (NO) content in blood of infertile patients and the therapeutic effect of integrative Chinese and western medicine (ICWM) treatment on the disease.

METHODSInfertile patients, 75 of AsAb positive and 68 of AsAb negative were selected to observe the mature partuient rate and abortion rate. Serum NO level were measured before treatment to observe the relationship between NO and positive AsAb. Patients were treated with ICWM and followed-up for five years.

RESULTSMean value of serum NO in patients with positive AsAb was significantly higher than that in fertile women, and there was no significant difference between patients with negative AsAb and fertile women (P < 0.01). In the 5 years after treatment, the mature partuient rate between the two groups showed insignificant difference (P > 0.05).

CONCLUSIONAsAb positive and NO level abnormal may interfere mutually, to intervent the reproductive process. ICWM therapy could effectively regulate auto-immunity and endocrine function, and make the infertile patients obtain satisfactory efficacy.

Adult ; Antibodies ; blood ; Dexamethasone ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Fertility Agents, Female ; therapeutic use ; Humans ; Infertility, Female ; blood ; drug therapy ; immunology ; Male ; Nitric Oxide ; blood ; Phytotherapy ; Spermatozoa ; immunology