Azalpenik gabeko gizonezkoen antzutasunaren oinarri molekularren azterketa

• Autores: Ainize Odriozola Larrañaga
• Directores de la Tesis: Nerea Subiran Ciudad (dir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2025
• Idioma: euskera
• Títulos paralelos:
  • Unravelling the molecular mechanisms of unexplained male infertility
• Programa de doctorado: Programa de Doctorado en Investigación Biomédica por la Universidad del País Vasco/Euskal Herriko Unibertsitatea
• Materias:
  • Ciencias médicas
• Enlaces
  • Tesis en acceso abierto en: ADDI
• Resumen

  • By transcriptomic and proteomic approaches, we identified significant alterations in energy metabolism associated processes in capacitated sperm from UMI patients compared to healthy donors, mainly in mitochondrial oxidative phosphorylation (OXPHOS). Functional assays validated these findings, revealing increased NADH and succinate dehydrogenase activity, which confirm disruptions in energy metabolism and redox balance in UMI patients. Furthermore, ART outcomes from the patients analyzed in this study demonstrated reduced ongoing pregnancy rates compared to donors, underscoring the clinical relevance of these metabolic disruptions.

    While our analysis of pooled UMI samples provided valuable insights into the potential mechanisms underlying UMI pathology, pooling samples may mask inter-individual variability in molecular and clinical profiles. To address this, we employed individualized transcriptomic approaches to validate findings from the pooled analyses. Our results confirmed that individual UMI patients exhibit mitochondrial-encoded transcriptome alterations in capacitated sperm, showing a downregulation of OXPHOS coding genes and an upregulation of non-coding genes.

    These findings suggest that mitochondrial dysfunction could be involved in UMI pathogenesis and in the impairment of fertilizing ability of the male gamete in UMI patients. To the best of our knowledge, this is the first study to analyze sperm transcriptomes from individual UMI patients, effectively overcoming the challenges posed by patient-to-patient heterogeneity. Importantly, this individualized approach enabled us to categorize UMI patients into two subgroups: donor-like and UMI-like, based on their transcriptomic similarity to sperm donor pools or to UMI patient pools with poor ART outcomes. Furthermore, we identified MT-RNR2 and RN7SKP203 as potential biomarkers for distinguishing UMI-like patients. In addition to transcriptomic insights, we explored other potential contributors to UMI. Characterization of anti-sperm antibody (ASA) patterns in seminal plasma revealed that research in the role of immune system in the male reproductive tract could also help uncover underlying causes of UMI.