ArticleCells2025
Advanced Paternal Age and Sperm Proteome Dynamics: A Possible Explanation for Age-Associated Male Fertility Decline.
Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Proteomic Landscape of Spermatozoa Under Inflammatory and Oxidative Injury: Molecular Mechanisms and Clinical Translation.Antioxidants (Basel, Switzerland) · 2026Review
- The effect of Covid-19 vaccines on semen parameters of patients undergoing infertility investigations: a self-controlled before-and-after study.Scientific reports · 2026Article
- Sperm DNA Fragmentation Is Associated with Impaired Directional Motility and Kinematic Efficiency: A CASA-Based Study.Medicina (Kaunas, Lithuania) · 2026Observational
- Association of paternal age with embryological outcomes and β-hCG positivity in women with polycystic ovary syndrome undergoing ICSI: a retrospective cohort study.Frontiers in medicine · 2026Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Male fertility is strongly influenced by environmental exposures, lifestyle, and advancing age. While advanced paternal age (APA) has been linked with a progressive decline in male fertility, poor reproductive outcomes, and decreased offspring health, the molecular mechanisms underlying these alterations remain unclear. In this work, we investigated the impact of men's age on human sperm protein expression and phosphorylation to identify molecular alterations possibly responsible for the age-associated decline in male fertility. Semen samples from volunteers attending fertility consultations at the Hospital of Aveiro were collected, analyzed according to WHO's guidelines, and processed by the density gradient technique. The proteome and phosphoproteome of 19 normozoospermic human sperm samples divided into four age groups were evaluated by mass spectrometry: ≤30 years old; 31-35 years old; 36-40 years old; and >40 years old. Proteomic analysis revealed 46 differentially expressed proteins (DEPs) between groups, some of them associated with infertility-related phenotypes. Gene ontology (GO) analysis, performed using the DAVID database, revealed that DEPs in older men were enriched in pathways related to stress response, metabolism, and embryo implantation. Additionally, 94 differentially phosphorylated sites corresponding to 76 differentially expressed phosphorylated proteins between the groups were identified, related to key reproductive processes such as sperm motility, spermatogenesis, and sperm binding to zona pellucida, and involved in metabolic and stress response pathways, like HSF1 activation. The set of proteins and phosphorylated residues altered in the sperm fraction usually used in assisted reproductive technology (ART) highlights the need to consider the age of the male partner during fertility assessment and treatment planning. These markers can also be used to explain cases of idiopathic infertility, failure in ART, or repeated abortion associated with APA, overcoming the subjectivity of the conventional semen analysis.
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Registered trials
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