Sperm proteomics: potential impact on male infertility treatment

ABSTRACT

Spermatozoa are unique cells that have highly compact DNA, motility (and hypermotility) patterns, a specific morphology, localized mitochondria and an apical acrosome. They are the end product of a dynamic process termed spermatogenesis. Sperm are therefore produced with specific proteins in order to effect different traits, such as the presence of cysteine-rich protamines in DNA, which effectively compacts DNA. Moreover, specific proteins are transferred during epididymal maturation and after ejaculation in order to render sperm capable of undergoing post-ejaculatory alterations, generally termed capacitation, which confers capacity to fertilize a mature oocyte. In addition, sperm exhibit several post-translational modifications, which are fundamental to their function, such as SUMOylation and ubiquitination. Discussed in this review is the current knowledge of the sperm proteome in terms of its composition and the function that these proteins determine, as well as their post-translational modifications and how these alter sperm functional integrity. Studies are emphasized that focus on shotgun proteomics – untargeted determination of the protein constituent of a cell in a given biological condition – and technologies currently applied toward that end are reviewed.

KEYWORDS:

• Sperm
• proteome
• male infertility
• human
• post-translational modifications
• LC-MS/MS

Acknowledgement

Financial support for this study was provided by the American Center for Reproductive Medicine, Cleveland Clinic.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Seminal improvement in MS and development of bioinformatics tools together with a renaissance in wet-bench aspects, such as 2D-gel electrophoresis, gel-free, and off-gel separation techniques have allowed proteomics to achieve its zenith.

• Proteomics is more promising for the study of sperm biology than other omics as these cells are essentially silent in terms of transcription and translation.

• A large number of spermatozoa proteins have been cataloged in various case-control studies.

• A set of proteins differentially expressed in spermatozoa of infertile patients point toward use of a set of biomarkers rather than a single protein.

• The spermatozoa proteome is a dynamic one and changes during post testicular stages enable sperm to fertilize the egg.

• Spermatozoal proteins undergo a series of post-translational changes during post-testicular maturation.

• Some proteins in spermatozoa undergo multiple post-translational modifications.

• Current trends that involve identifying PTMs are only predictive.

• Studying protein interactions and the structures of multi-protein complexes may shed more light on the different proteins involved in sperm function.