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PMID: 40649876 Published · epublish English Journal Article

Age-Associated Proteomic Changes in Human Spermatozoa.

International journal of molecular sciences ·Vol. 26 ·No. 13 ·2025-06-25

Beg MA, Ismail AO, Alaiya A, Khan FA, Hamoda TAA, Sheikh IA, Sharma P, Baothman OM, Alkhzaim AH, Shinwari Z, Abuzinadah RF, Mohammed A, Assiri AM, Abuzenadah AM, Memili E, Feugang JM

Abstract

Advancing age in men significantly contributes to declining sperm fertility. Information on age-related proteomic changes in spermatozoa is limited. This study involved normal fertile Arab men in three age groups: young adult (21-30 years; n = 6), late adult (31-40 years; n = 7), and advanced age (40-51 years; n = 5). Gradient-purified spermatozoa were analyzed using LC-MS/MS and proteomic data were processed using Progenesis QI (QIfp) v3.0 and UniProt/SwissProt. Significantly enriched annotations and clustering of proteins in the proteomic datasets were identified (2-fold change; p < 0.05). A total of 588 proteins were identified, with 93% shared across the three groups. Unique proteins were MYLK4 for the young adult group, PRSS57 for the late adult group, and HMGB4, KRT4, LPGAT1, OXCT2, and MGRN1 for the advanced age group. Furthermore, 261 (44%) proteins were differentially expressed (p < 0.05) across the three groups. Functional enrichment analysis suggested an aging-related significant increase in pathways associated with neurodegenerative diseases and protein folding, alongside decreases in glycolysis/gluconeogenesis, flagellated sperm motility, acetylation, phosphoprotein modifications, oxidation processes, and Ubl conjugation. Cluster analysis highlighted significantly upregulated proteins in young adults (e.g., H2BC1, LAP3, SQLE, LTF, PDIA4, DYNLT2) and late adults (e.g., ATP5F1B, ODF2, TUBA3C, ENO1, SPO11, TEX45, TEKT3), whereas most proteins in the advanced age group exhibited downregulation (e.g., SPESP1, RAB10, SEPTIN4, RAB15, PTPN7, USP5, ANXA1, PRDX1). In conclusion, this study revealed aging-associated proteomic changes in spermatozoa that impact critical processes, including spermatogenesis, motility, metabolism, and fertilization, potentially contributing to fertility decline. These changes provide a molecular framework for developing therapies to preserve sperm proteostasis and enhance fertility in older men.

Keywords
LC-MS/MS aging human proteomics spermatozoa
MeSH Terms
Humans Male Spermatozoa/metabolism Adult Proteomics/methods Aging/metabolism Middle Aged Proteome/metabolism Young Adult Sperm Motility Tandem Mass Spectrometry
Chemicals
Proteome
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Beg Mohd Amin ORCID
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Ismail Abrar Osama
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. | Biomedical Sciences, Clinical Embryology and Reproductive Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Alaiya Ayodele ORCID
Cell Therapy & Immunobiology Department, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Khan Firdous Ahmad ORCID
Department of Large Animal Medicine and Surgery, School of Veterinary Medicine, St. George's University, True Blue, Grenada.
Hamoda Taha Abo-Almagd Abdel-Meguid ORCID
Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Sheikh Ishfaq Ahmad
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Sharma Priyanka
Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Baothman Omar Mohammed
Microbiology and Molecular Section, Al Salama Hospital, Jeddah 23611, Saudi Arabia.
Alkhzaim Ali Hasan
Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Shinwari Zakia ORCID
Cell Therapy & Immunobiology Department, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Abuzinadah Rinad Fahad
Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Mohammed Arif
Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 23890, Saudi Arabia.
Assiri Abdullah Mohammed ORCID
Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Abuzenadah Adel Mohammad
King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia. | King Faisal University, Hufof 36362, Saudi Arabia.
Memili Erdogan
Cooperative Agricultural Research Center, College of Agriculture and Human Sciences, Prairie View A&M University, Prairie View, TX 77446, USA.
Feugang Jean Magloire ORCID
Department of Animal and Dairy Sciences, Mississippi State University, Starkville, MS 39759, USA.
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Article Info
Journal
International journal of molecular sciences
Abbr.
Int J Mol Sci
ISSN
1422-0067
DOI
10.3390/ijms26136099
Published
2025-06-25
Epub
2025-00-25
Language
English
Region
Switzerland
NLM ID
101092791
PMCID
PMC12249680
Subset
IM
Grants
Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia · 1132
External Links
PubMed source DOI: 10.3390/ijms26136099 PMC Full Text View journal details
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