The Molecular Biomarkers of Sperm Fitness

Cohen, Jayme (2025) The Molecular Biomarkers of Sperm Fitness. Doctoral thesis, University of East Anglia.

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Abstract

Sperm are among the most specialised and variable cell types in the animal body, differing not only across species but also between and within individuals. This molecular and phenotypic diversity has important implications for fertility, yet the mechanisms generating variation among sperm and their evolutionary and clinical consequences remain poorly understood. This thesis combines quantitative proteomics, bioinformatics, and single-cell analysis to investigate how environmental and physiological stress shape sperm phenotype and to test whether molecular heterogeneity within ejaculates provides a substrate for haploid selection. In Chapter 1, tandem mass tag proteomics revealed that acute heat stress in zebrafish (Danio rerio) testes induces a coordinated shift in the proteome, with depletion of proteins linked to spermatogenesis and motility and enrichment of chaperones and stress-response factors, demonstrating dynamic germline remodelling under environmental challenge. Chapter 2 presents a comprehensive zebrafish sperm proteome that establishes a baseline for functional and comparative work and shows that stress-induced testicular changes translate into altered sperm protein composition. In Chapter 3, fractionation of human ejaculates by swim-up and methyl-cellulose migration revealed consistent proteomic differences between higher- and lower-fitness sperm subpopulations, identifying candidate surface biomarkers of sperm quality. Chapter 4 validated two of these candidates, OLFM4 and CTNG, as accessible on the sperm surface and inversely associated with sperm longevity using spectral imaging flow cytometry. Together, these studies demonstrate that sperm phenotypes reflect underlying molecular differences that can be detected, quantified, and linked to fitness-related traits. They provide molecular evidence for haploid selection acting within ejaculates and establish a translational foundation for biomarker-based sperm assessment in assisted reproduction.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	28 Jan 2026 10:30
Last Modified:	28 Jan 2026 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101761
DOI:

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