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Pini, T.* ; Nixon, B.* ; Timothy L, K.* ; Teperino, R. ; Sanz-Moreno, A. ; da Silva Buttkus, P. ; Tüttelmann, F.* ; Kliesch, S.* ; Gailus-Durner, V. ; Fuchs, H. ; Marschall, S. ; Hrabě de Angelis, M. ; Skerrett-Byrne, D.A.

Towards a kingdom of reproductive life - the core sperm proteome.

Reproduction 169:e250105 (2025)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Reproductive biology is often considered in three siloed research areas; humans, agriculture and wildlife. Yet, each demand solutions for treatment of subfertility, fertility biomarkers, development of assisted reproductive technologies and effective contraception. To efficiently develop solutions applicable to all species, we must improve our understanding of the common biology underpinning reproductive processes. Accordingly, we integrate proteomic data from 29 publicly available datasets (>2 TB of data) to characterize mature sperm proteomes spanning 12 vertebrate species, identifying 13,853 proteins. Although human and mouse have relatively wellannotated sperm proteomes, many non-model species rely heavily on predicted or homologyinferred identifications. Despite variation in proteome size, composition and reproductive strategies, comparative analyses revealed that vertebrates share a fundamental molecular framework essential for sperm function. A core set of 45 species-level and 135 order-level conserved proteins mapped to critical processes, including energy generation, acrosome function, as well as novel signalling pathways (BAG2 and FAT10). Knockout mouse models further validate the significance of these conserved proteins, demonstrating that their disruption impairs sperm motility and fertilization capacity. Moreover, we discovered loss-of-function variants of two additional core sperm proteins in clinical samples, linking them to severe sperm defects. Intriguingly, in-silico analysis reveals function-driven, context-dependent diversity surpassing evolutionary patterns. Collectively, these results highlight the value of integrating publicly available datasets and underscore the need for improved genome/proteome annotation in nonmodel species in mammals. This work provides a foundation for developing cross-species strategies to enhance fertility treatments, assisted reproductive technologies, and conservation efforts.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter sperm; sperm proteome; fertility; data reanalysis; Pebp4; Echs1; Etfb; Ndufa10; Aldh7a1; proteomics; bioinformatics; Human Seminal Plasma; Interactive Tree; A2 Hspa2; Spermatozoa; Proteins; Storage; Gene; Phosphorylation; Differentiation; Identification
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1470-1626
e-ISSN 1741-7899
Zeitschrift Reproduction
Quellenangaben Band: 169, Heft: 6, Seiten: , Artikelnummer: e250105 Supplement: ,
Verlag BioScientifica
Verlagsort Bristol
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500693-001
G-500692-001
G-500600-001
Förderungen German Federal Ministry for Education and Research (BMBF) as part of the Junior Scientist Research Centre 'Repro Track MS
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Clinical Research Unit' Male Germ Cells
College of Engineering, Science and Environment (University of Newcastle) Accelerator Fellowship
National Health and Medical Research Council of Australia (NHMRC) Emerging Leadership Fellowship
DOI 10.1530/REP-25-0105
WOS ID 001529619000008
PubMed ID 40298292
Erfassungsdatum 2025-05-05
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