Advances in sperm proteomics: best-practise methodology and clinical potential

Abstract

The recent application of mass spectrometry to the study of the sperm cell has led to an unprecedented capacity for identification of sperm proteins in a variety of species. Knowledge of the proteins that make up the sperm cell represents the first step towards understanding its normal function and the molecular anomalies associated with male infertility. The present review starts with an introduction of the sperm cell biology and is followed by the consideration of the methodological key aspects to be aware of during sample sourcing and preparation, including data interpretation. It then overviews the initiatives developed so far towards the completion of the sperm proteome, with a particular focus in human but with the inclusion of some comments on different model species. Finally, all studies performing differential proteomics in infertile patients are reviewed, pointing to future potential applications.

Keywords:

• chromatin
• epigenetics
• genomics
• protamines
• proteome
• proteomics
• sperm
• spermatozoa

Financial & competing interests disclosure

The Proteomic Unit of the Scientific and Technological Centres of the University of Barcelona (CCiTUB) is a member of the ProteoRed network (http://www.proteored.org/). This work was supported by grants to R Oliva from the Spanish Ministry of Economy and Competitiveness (Ministerio de Economia y Competitividad; FEDER BFU 2009-07118 and PI13/00699) from Fundación Salud 2000 (SERONO 13-015), and from EU-FP7-PEOPLE-2011-ITN289880. The authors have no other 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 apart from those disclosed.

Key issues

• Proteomic analysis of the human sperm has so far provided a catalogue of 6198 proteins and it can be predicted from pathway analysis that the complete human sperm proteome will be composed of at least 7500 proteins.

• The sperm cell proteome of many different model species is currently being uncovered and is revealing conserved trends and clues of the key functionally relevant proteins.

• Data mining of the sperm proteome is revealing new functional and metabolic insights. For example, some metabolic pathways in sperm may be more preponderant than previously thought. Also it is now clear that the mature sperm cell from different species, including human delivers to the oocyte, many chromatin associated proteins, in addition to protamines and histones, with the potential of delivering a wealth of epigenetic information.

• Proteomic analysis is identifying proteins increased or decreased in different types of infertile patients and in different conditions in animal models. These proteins have the potential to be useful as diagnostic or prognostic markers.

• The challenge is now to fully understand the function of the different proteins making up the sperm cell, and uncover the relationship between the sperm proteome, transcriptome, chromatin structure, epigenome, metabolome and genome in health and disease from a systems biology approach.

Notes