Human prostasomes from normozoospermic and non‐normozoospermic men show a differential protein expression pattern

Abstract

Prostasomes are exosomes such as extracellular vesicles, produced in the prostatic epithelium and released into the seminal plasma, that play an important role enhancing male fertility. Although some studies have demonstrated that prostasomes have a rich proteomic content, it is still unclear if that proteomic content varies depending on the male fertility status. Prostasomes from 12 normozoospermic and 14 non-normozoospermic seminal samples were isolated by differential ultracentrifugation. Protein content was studied by quantitative mass spectrometry and compared between both cohorts. We identified 1282 proteins with 745 of them (57.8%) being present in all seven prostasome pools. Forty-seven of those commonly present proteins showed differential expression levels in both cohorts. Specifically, prostasomes from non-normozoospermic samples showed a pattern of protein underexpression for a group of proteins including several proteins from the spermatozoa's energy production pathways as well as some proteins directly implicated in sperm activity. Variations in prostasomal protein content levels may have a relevant correlation with male fertility and thus could be of great utility as a biomarker of fertility status.

Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility

“…Prostasomal proteins have antioxidant, antimicrobial and antibacterial properties; coagulant properties serve to prevent sperm contact with female blood, and protect SPZ against the immune response in the female reproductive tract by inhibiting monocyte and neutrophil phagocytosis [ 22 , 64 , 75 ]. Additionally, these vesicles play key roles, both inhibitory and stimulatory, in several physiological sperm functions, such as sperm motility, sperm capacitation and acrosome reaction [ 62 , 76 ].…”

“…In this regard, under physiological conditions, increased progesterone levels stimulate prostasome and sperm membrane fusion [ 5 ]. Furthermore, prostasomes are able to prevent an early acrosomal reaction by transferring to sperm membrane cholesterol and sphingomyelin [ 22 ].…”

“…Semen analysis is the most widely technique used to determine male fertility, but it has become evident that, in many cases, a basic seminogram is insufficient to determine the fertility status of the male partner. In this context, the SP and, particularly, its proteome profile, offers a great opportunity to increase our knowledge of the physiology of the male reproductive system and for the discovery of biomarkers to improve diagnosis or classification of a wide range of male fertility disorders [ 3 , 22 , 23 , 35 ].…”

“…SP proteins are also involved in the regulation of sperm motility, hyperactivation and acrosomal reaction; they provide protection against oxidative processes and have immunosuppressive properties inducing an effective inhibition of lymphocytes, macrophages and the complement system [ 2 , 5 , 6 , 10 , 22 , 64 , 91 , 92 , 93 ]. SP has the additional advantage that it is usually obtained in large amounts, providing a good source for proteomic analysis.…”

“…Although the transfer of proteins to SPZ represents a common feature of seminal exosomes, it is actually discussed whether distinct populations of vesicles carry out different tasks [ 22 , 23 ]. Whatever the case, the analysis of seminal proteome has corroborated the involvement of this fluid in the control of sperm physiology [ 24 ], motility [ 25 ], morphology [ 26 ], concentration [ 27 ] and protection from oxidation [ 28 ].…”