Bringing proteomics to bear on male fertility: key lessons

ABSTRACT

Introduction

Male infertility is a major public health concern globally. Proteomics has revolutionized our comprehension of male fertility by identifying potential infertility biomarkers and reproductive defects. Studies comparing sperm proteome with other male reproductive tissues have the potential to refine fertility diagnostics and guide infertility treatment development.

Areas covered

This review encapsulates literature using proteomic approaches to progress male reproductive biology. Our search methodology included systematic searches of databases such as PubMed, Scopus, and Web of Science for articles up to 2023. Keywords used included ‘male fertility proteomics,’ ‘spermatozoa proteome,’ ‘testis proteomics,’ ‘epididymal proteomics,’ and ‘non-hormonal male contraception.’ Inclusion criteria were robust experimental design, significant contributions to male fertility, and novel use of proteomic technologies.

Expert Opinion

Expert analysis shows a shift from traditional research to an integrative approach that clarifies male reproductive health’s molecular intricacies. A gap exists between proteomic discoveries and clinical application. The expert opinions consolidated here not only navigate the current findings but also chart the future proteomic applications for scientific and clinical breakthroughs. We underscore the need for continued investment in proteomic research – both in the technological and collaborative arenas – to further unravel the secrets of male fertility, which will be central to resolving fertility issues in the coming era.

KEYWORDS:

• Male infertility
• sperm proteome
• testicular proteomics
• epididymal proteomics
• proteomic biomarkers
• post-translational modifications
• male reproductive proteome
• fertility diagnostics

Article highlights

• Proteomics has unveiled a detailed landscape of the sperm proteome, revealed molecular determinants of male fertility, and facilitated new avenues for the diagnosis and treatment of male infertility.

• Advances in mass spectrometry-based proteomics have enabled the identification of essential proteins and pathways involved in spermatogenesis, sperm maturation, and fertilization.

• Proteomic studies have highlighted the significant role of the epididymis in sperm maturation, with the identification of epididymosome-related proteins contributing to our understanding of sperm cell communication and maturation processes.

• Emerging proteomic technologies, such as targeted proteomics and multiplexed quantitative approaches, are heralding a new era of precision in the analysis of the male reproductive proteome.

• This review synthesizes pivotal findings from proteomic research, drawing connections between emerging scientific knowledge and potential clinical applications in the field of male reproductive health.

Abbreviations

a disintegrin and metalloproteinase (ADAM), affinity purification followed by mass spectrometry (AP-MS), A-kinase anchoring protein (AKAP), assisted reproductive technologies (ART), Chromosome-Centric Human Proteome Project (C-HPP), density gradient centrifugation (DC), detergent-resistant membranes (DRMs), enzyme-linked immunosorbent assay (ELISA), false-positive rate (FPR), fibronectin (FN1), fumarate hydratase (FH), gamma-glutamylhydrolase (γ-GH), Gene Ontology (GO), glyceraldehyde-3-phosphate dehydrogenase (GAPDHS), Heterozygous (HET), Human Testis Proteome Database (HTPD), hyaluronic acid (HA), hypospermatogenesis (Hyp), immobilized pH gradient (IPG), immunoprecipitation of proteins coupled with mass spectrometry (IP-MS), in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), isobaric Tags for Relative and Absolute Quantitation (iTRAQ), knockout (KO), liquid chromatography-tandem mass spectrometry (LC-MS/MS), male factor infertility (MFI), mass spectrometry (MS), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS), Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF), Missing proteins (MPs), multiple reaction monitoring (MRM), Non-obstructive azoospermia (NOA), obstructive azoospermia (OA), oligoasthenoteratozoospermia (OAT), oligoasthenozoospermia (OA), one-dimensional gel electrophoresis (1-DE), post-translational modification (PTM), post-vasectomy (PV), protein existence (PE), protein-protein interactions (PPI), proximity labeling (PL), proximity-dependent biotin identification (BioID), quantitative polymerase chain reaction (qPCR), reactive oxygen species (ROS), selected reaction monitoring (SRM), Sertoli cell-only syndrome (SCO), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), swim-up (SU), tandem mass tag (TMT), testicular germ cells (TGCs), the citrate cycle (TCA cycle), titanium dioxide (TiO2), transmembrane helix (TMH), two-dimensional gel electrophoresis (2-DE), ultra-high performance liquid chromatography (UHPLC), unexplained male infertility (UMI), Western blotting (WB), zona pellucida (ZP)

Declaration of interest

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, patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer on this manuscript received an honorarium from Expert Review of Proteomics for their review work but have no other relevant financial relationships to disclose. The remaining reviewers have no other relevant financial relationships or otherwise to disclose

Author contributions

R Parkes performed the literature search. R Parkes and TX Garcia wrote the manuscript. All authors read and approved the final manuscript.

Acknowledgments

This study has been supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grants R01HD095341 (to T.X.G.), R01HD106056 (to T.X.G.); Male Contraceptive Initiative Grant 2021-302 (to T.X.G.).

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14789450.2024.2327553

Additional information

Funding

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grants R01HD095341 (to TX Garcia), R01HD106056 (to TX Garcia); Male Contraceptive Initiative Grant 2021-302 (to TX Garcia).