Extracellular vesicle cargo of the male reproductive tract and the paternal preconception environment

Abstract

The molecular composition of extracellular vesicles (EVs) is emerging as a novel biomarker in many areas of research including reproductive health. EVs transport biological molecules such as RNA and protein to facilitate cell-to-cell communication among cells of the male reproductive tract. Human and animal studies have shown that EVs present in seminal plasma or in the male reproductive tract contain important cargo that are important for successful reproductive outcomes. Small non-coding RNAs (sncRNA) have been at the forefront of this research, and as such, they have the potential to serve as novel biomarkers of male infertility diagnosis and reproductive success. This review provides an overview of EV biosynthesis and examines the molecular payloads of seminal plasma EVs on male infertility and reproductive success as well as future research that is warranted to examine how these molecular payloads may be modified by environmental factors.

Keywords: Extracellular vesicles; environment; exosomes; male reproductive health; preconception; seminal plasma; small noncoding RNA; sncRNA.

Figure 1.

EV structure and biogenesis. (A) Exosome image cryo-electron microscopy image of a seminal plasma EV isolated by the differential ultracentrifuge. (B) Exosome biogenesis. Proteins released from the trans-Golgi network and RNA molecules destined to the plasma membrane shed as microvesicles. Exosomes originate from Multivesicular bodies (MVBs). Endosomes mature into MVBs and intravaginal budding results in the formation of intraluminal vesicles (ILVs). In some cases, MVB fuse into the plasma membrane and release ILVs to the extracellular region as exosomes. (C) Exosome structure. Exosomes have protein and RNA that play a critical role in intercellular communication. Tetraspanins (CD9, CD63, CD81, CD82) and Heat-shock proteins (HSP70, HSP90) are distinct proteins commonly used for exosome characterization. Signaling proteins (EGFR, PI3K, HIF-1α, β- Catenin) and MVB proteins are sourced from inward budding of ILVs. Exosomes also have some proteins (MHC I) and lipids (cholesterol, sphingolipids, ceramides) from cellular membrane and RNA cargo (mRNA and miRNA) which function as a post-transcriptional alteration in gene expression.