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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, DOI: 10.1530/REP-25-0105 (2025)
Postprint DOI PMC
Open Access Green
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
Korrespondenzautor
ISSN (print) / ISBN 1470-1626
e-ISSN 1741-7899
Zeitschrift Reproduction
Verlag BioScientifica
Verlagsort Bristol
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)