Tu170 - Dysregulated Lymphocytes in Infertile Men: Potential Biomarkers for Non-communicable Disease Development

Abstract Text: Infertile men are at high risk of developing age-related non-communicable diseases (NCDs). Infertile men diagnosed with OligoAsthenoTeratozoospermia (OAT) and Non-Obstructive Azoospermia (NOA) are characterized by a pro-inflammatory milieu with increased frequency of myeloid cells and reduced T cells, which are immune alterations typically observed in healthy elderly men. Distinct T cell signatures of exhaustion and senescence discriminate the two infertile conditions. With the goal of identifying biomarkers to monitor and potentially predict the development of NCDs in infertile men, we further characterized the lymphoid compartments in a larger cohort of patients.
While the proportion of lymphoid cells in infertile is reduced compared to that of fertile men, T cells, specifically in OAT patients, are characterized by the expression of the exhaustion markers TIGIT/LAG-3/Eomes/PD-1 alone or in combination. Moreover, a high proportion of T cells in NOA, but not in OAT patients, expressed high levels of the fluorescent senescent-associated--Galactosidase marker. A reduced total and naïve B cell frequency, associated with an increased proportion of antibody-secreting cells, both plasma blasts and plasma cells, and of autoreactive cells, is also observed in infertile men, suggesting the hyperactivation of B cells in infertile patients.
These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures. More broad correlation analysis of the immunological status, in association with clinical parameters and genomic and transcriptomic data, will define specific signatures to better identify patients at higher risk of earlier developing NCDs and will be instrumental in developing personalized secondary preventive strategies.