Abstract

Infertility has become a global health issue, with approximately 50% of infertility cases generated by disorders in male reproduction. Spermatozoa are conveyed towards female genital tracts in a safe surrounding provided by the seminal plasma. Interestingly, this dynamically changing medium is a rich source of proteins, essential not only for sperm transport, but also for its protection and maturation. Most of the seminal proteins are acquired by spermatozoa in transit through exosomes (epididymosomes and prostasomes). The high number of seminal proteins, the increasing knowledge of their origins and biological functions and their differential expression in the case of azoospermia, asthenozoospermia, oligozoospermia and teratozoospermia or other conditions of male infertility have allowed the identification of a wide variety of biomarker candidates and their involvement in biological pathways, thus to strongly suggest that the proteomic landscape of seminal plasma may be a potential indicator of sperm dysfunction. This review summarizes the current knowledge in seminal plasma proteomics and its potentiality as a diagnostic tool in different degrees of male infertility.

Highlights

  • Spermatozoa (SPZ) are streamlined cells, optimized to propagate their haploid genome by exploiting the egg

  • The high number of seminal proteins, the increasing knowledge of their origins and biological functions and their differential expression in the case of azoospermia, asthenozoospermia, oligozoospermia and teratozoospermia or other conditions of male infertility have allowed the identification of a wide variety of biomarker candidates and their involvement in biological pathways, to strongly suggest that the proteomic landscape of seminal plasma may be a potential indicator of sperm dysfunction

  • What is interesting is that seminal plasma (SP) is enriched in proteins, RNAs and lipids that are present in the fluid and/or encapsulated in extracellular vesicles or exosomes

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Summary

Introduction

Spermatozoa (SPZ) are streamlined cells, optimized to propagate their haploid genome by exploiting the egg. Since the complexity of the SP composition, it is evident that it has not just the function of sperm transport [2] Along both male and female reproductive tracts, SPZ encounter a novel extracellular milieu, able to modulate their metabolism, their intracellular structures and biochemical composition, through an intense communication that mainly occurs via exosomes [12]. The seminal proteomic profile may be indicative of genital tract dysfunctions and, serve as a biomarker of infertility [3,10,35,36] In this regard, exosomes isolated from SP of normo-, astheno- and azoospermic patients display similar features in terms of shape, size and expression of typical exosomal markers, they differ in their cargo. Much effort is required to deeply unveil (i) the molecular composition of SP and, of seminal exosomes, (ii) who regulates vesicle trafficking and fusion with SPZ and (iii) which are the precise exosomal functions in sperm physiology

Exosomes in the Male Reproductive Tract
The SP Proteome
Analysis of Human SP Proteome
SP Candidate Biomarkers of Male Infertility
SP Candidate Biomarkers for Azoospermia
SP Candidate Biomarkers for Varicocele
SP Candidate Biomarkers for Primary and Secondary Infertility
Findings
Conclusions and Future Perspectives
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