IMMUNOLOGICAL CHARACTERIZATION OF SEVERE INFERTILE MEN REVEALED ALTERATIONS OF THE LYMPHOID AND MYELOID COMPARTMENTS

Background: Infertility is the inability of a sexually active, non-contraceptive couple to achieve spontaneous pregnancy in one year. It is estimated to affect worldwide up to 15% of couples; overall, a male infertility factor has been found in at least 40% of infertile couples. Several studies have shown that infertile men have a higher incidence and prevalence of cancer, chronic non-malignant morbidities, endocrinological and autoimmune disorders, and overall a higher mortality risk compared to fertile age-matched men. Various hypotheses have been considered to explain the factors underlying male health status and male factor infertility, including genetic, endocrinological, and metabolic abnormalities. Recent evidence has shown that the immune testicular cells are different among infertile and fertile individuals. Testicular tissue of infertile men showed a pro-inflammatory phenotype which was not found in fertile controls. Moreover, a senescent phenotype was observed in azoospermic somatic cells of infertile men but not in those from the control group. The previously reported findings in infertile men documented a shift from the immune-privileged status to a proinflammatory testicular environment, eventually associated with iNOA. From a translational point of view, the pro-inflammatory status of testicular cells and the senescent phenotype characterized by decreased T cells number and higher level of inflammatory cytokines observed in infertile men could be associated with the infertility status per se, an exhausted pattern of circulating immune cells and it could predispose to future risk of developing malignancies and chronic diseases. However, a detailed characterization of the local (e.g. testicular) and systemic immune status of infertile and fertile men has never been investigated. Our main hypothesis that infertile men have alterations/defect of the immune system has been pursued with the following specific aims: AIM 1. To assess lymphoid and myeloid cell distribution in seminal fluid and peripheral ...