Immune mediators associated to male infertility in a mouse model of DNA immunization with the sperm protease proacrosin

• CF1 male mice DNA immunization with human proacrosin induced specific high IgG levels in serum and seminal vesicle fluid.
• Fertility was impaired and inversely correlated with anti-proacrosin antibodies.
• Expression of IL-10 and TGF-β1 was reduced in the testis.
• Expression of TNF-α and IFN-γ was increased in the seminal vesicles.
• Immunized animals had fewer pups born than controls.

The immune response has relevant physiological functions both in the male and female reproductive system, and must be tightly controlled to achieve a successful pregnancy. Several immune factors have been related to infertility, among them humoral and cellular immune responses triggered by sperm antigens. The present study was aimed at evaluating the immune profile induced by DNA immunization against the sperm protease proacrosin in CF1 male mice and its effect upon fertility.Immunized animals exhibited higher anti-proacrosin antibodies levels than controls (indirect ELISA), both in serum (p < 0.01) and in seminal vesicle fluid (SVF; p < 0.05). IgG2a levels were higher than IgG1 in serum (p < 0.01) and similar in SVF. IL-10 and TGF-β1 mRNA levels were lower in testis (p < 0.05), whereas TNF-α and IFN-γ transcript levels were increased in SV tissue (p < 0.05). Immunized mice showed a trend toward higher IFN-γ concentration in serum and SVF than controls. Male fertility rate was diminished in immunized mice (p < 0.01) and inversely correlated with serum and SVF anti-proacrosin IgG levels (p < 0.001). Immunized animals also had fewer pups born than controls (p < 0.01).To our knowledge, this is the first report on DNA immunization done in CF1 mice. Injection of proacrosin DNA induces an immune response in the male reproductive tract characterized by high levels of specific antibodies and cytokine changes. These factors may alter the crucial balance of the genital tract microenvironment required for adequate fertilization and pregnancy.