Abstract |
Male infertility refers to the inability of a male to achieve pregnancy upon complication with a fertile female and accounts for the 40 - 50% of infertile cases. Usually, male infertility is associated with sperm quality, which is influenced by a number of factors. Immunological factors probably contribute to a substantial number of cases of unexplained infertility, while immunity appears to regulate ejaculation quality and fertility in humans. The specificity of spermatozoa, compared to other body cells, to develop in an immunologically privileged site, makes them susceptible to autoimmune and other immune reactions. The major histocompatibility complex is involved in all these immune responses and therefore plays a key role in the process of fertilization.
The first aim of this project was to detect the expression of classical and non classical major histocompatibility complex class II antigens (DR, DM, DO, CD74) on the membrane and cytoplasm of sperm, and correlate them to the sperm parameters determined by semen analysis to assess the overall quality of sperm. Immunofluorescence experiments detected the presence of all HLA class II studied. The expression profiles of these antigens appeared to vary from sample to sample, while there was good correlation between the presence of specific antigens and specific parameters of semen analysis. Interestingly, RT-PCR analysis detected a new pattern of gene expression in sperm which differs from the up to now known expression systems. Therefore, based on the histocompatibility antigens studied here, it can be safely concluded that these could be used as novel diagnostic tests for investigating unexplained infertility, as well as the selection of the fertilization gamete.
The second aim of this project was to determine the levels of inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IFN-c and TNF-a), in the seminal plasma of the same samples. The obtained results did not show any direct correlation with the presence of these histocompatibility antigens, but the presence of specific cytokines associated with sperm quality.
Finally, in the present work, the levels of soluble class II histocompatibility antigens in the seminal plasma was determined and cottelated to semen quality. The results detected a good correlation between the presence of membrane and soluble class II histocompatibility antigen on sperm and seminal plasma respectively, which was also correlated with sperm quality, enabling thus their future use as indicators of quality and fertility of sperm.
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