New Insights on Sperm Function in Male Infertility of Unknown Origin: A Multimodal Approach
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Published:2023-09-27
Issue:10
Volume:13
Page:1462
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ISSN:2218-273X
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Container-title:Biomolecules
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language:en
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Short-container-title:Biomolecules
Author:
Pacheco Rita I.1, Cristo Maria I.12, Anjo Sandra I.12ORCID, Silva Andreia F.12ORCID, Sousa Maria Inês13, Tavares Renata S.13, Sousa Ana Paula145, Almeida Santos Teresa1456ORCID, Moura-Ramos Mariana4578ORCID, Caramelo Francisco6ORCID, Manadas Bruno12ORCID, Ramalho-Santos João13ORCID, Amaral Sandra Gomes12
Affiliation:
1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal 2. IIIUC—Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal 3. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000-456 Coimbra, Portugal 4. Reproductive Medicine Unit, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal 5. Eugin Coimbra, Rua Filipe Hodart 12, 3000-185 Coimbra, Portugal 6. Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal 7. Center for Research in Neuropsychology and Cognitive and Behavioral Intervention, Faculty of Psychology and Educational Sciences, University of Coimbra, 3000-115 Coimbra, Portugal 8. Clinical Psychology Unit, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal
Abstract
The global trend of rising (male) infertility is concerning, and the unidentifiable causes in half of the cases, the so-called unknown origin male infertility (UOMI), demands a better understanding and assessment of both external/internal factors and mechanisms potentially involved. In this work, it was our aim to obtain new insight on UOMI, specifically on idiopathic (ID) and Unexplained male infertility (UMI), relying on a detailed evaluation of the male gamete, including functional, metabolic and proteomic aspects. For this purpose, 1114 semen samples, from males in couples seeking infertility treatment, were collected at the Reproductive Medicine Unit from the Centro Hospitalar e Universitário de Coimbra (CHUC), from July 2018–July 2022. Based on the couples’ clinical data, seminal/hormonal analysis, and strict eligibility criteria, samples were categorized in 3 groups, control (CTRL), ID and UMI. Lifestyle factors and anxiety/depression symptoms were assessed via survey. Sperm samples were evaluated functionally, mitochondrially and using proteomics. The results of Assisted Reproduction Techniques were assessed whenever available. According to our results, ID patients presented the worst sperm functional profile, while UMI patients were similar to controls. The proteomic analysis revealed 145 differentially expressed proteins, 8 of which were specifically altered in ID and UMI samples. Acrosin (ACRO) and sperm acrosome membrane-associated protein 4 (SACA4) were downregulated in ID patients while laminin subunit beta-2 (LAMB2), mannose 6-phosphate isomerase (MPI), ATP-dependent 6-phosphofructokinase liver type (PFKAL), STAR domain-containing protein 10 (STA10), serotransferrin (TRFE) and exportin-2 (XPO2) were downregulated in UMI patients. Using random forest analysis, SACA4 and LAMB2 were identified as the sperm proteins with a higher chance of distinguishing ID and UMI patients, and their function and expression variation were in accordance with the functional results. No alterations were observed in terms of lifestyle and psychological factors among the 3 groups. These findings obtained in an experimental setting based on 3 well-defined groups of subjects, might help to validate new biomarkers for unknown origin male infertility (ID and UMI) that, in the future, can be used to improve diagnostics and treatments.
Funder
European Regional Development Fund National Mass Spectrometry Network FCT
Subject
Molecular Biology,Biochemistry
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