The transformative impact of extracellular vesicles on developing sperm

Abstract

Objective To review the role of extracellular vesicles (EVs) released from the male reproductive tract and their impact on developing sperm. We discuss how sperm exiting the seminiferous tubules, although developmentally mature, require further modification. Acquisition of various functions including increased motility, transfer of cargoes and ability to undertake the acrosome reaction are mediated through the interaction between sperm and EVs. Methods A review of the literature identified that EVs are released from different portions of the male reproductive tract, notably the epididymis and prostate. These EVs interact with sperm as they pass from the seminiferous tubules to the epididymis and vas deferens prior to ejaculation. Results EVs are small lipid bound particles carrying bespoke RNA, protein and lipid cargoes. These cargoes are loaded based on the state of the parent cell and are used to communicate with recipient cells. In sperm, these cargoes are essential for post testicular modification. Sperm extracted from the proximal epididymis are poorly motile and unable to carry out the acrosome reaction. Conclusions Interaction between developing sperm and EVs is important for the subsequent function of sperm. Little is known however about EVs released from the seminiferous tubules to developing sperm or in the fetal and pre-pubertal testes. A greater understanding, especially in the formation and development of the spermatogonial stem cell niche may lead to new insights as to how damage to this niche may be prevented and preserve future fertility.

Exosomes: New regulators of reproductive development

“…Exosomes mediate numerous modifications and gains when sperm leave the testes and get into the epididymis [ [26] , [27] , [28] , [29] ]. The cargo of epididymosomes derives from epididymal fluid, caudal and distal have differential cargo loading [ 30 ]. Epididymal caput, corpus and cauda derived exosomal proteins are related to motility (cSrc and MIF), fertilization (SPAM1, GliPr1L1 and Metalloproteases) and acrosome reaction (Liri α3) [ 31 ].…”

“…Exosomes mediate numerous modifications and gains when sperm leave the testes and enter the epididymis [ [26] , [27] , [28] , [29] ]. In human, bovine and mouse models, the cargo of epididymosomes derives from epididymal fluid, epididymal cauda and caput have differential cargo loading respectively [ 30 ]. In a cat model, epididymal caput, corpus and cauda derived exosomal proteins are related to motility, zona pellucida binding and acrosome reaction, and have been linked to teratospermia [ 31 ].…”

Extracellular vesicles from seminal plasma to improve fertilizing capacity of bulls

“…Inside the seminal plasma there are extracellular vesicles (EVs) that could be important vehicles of endogenous molecules that, with exogenous factors (chemicals, environmental stressor, ect. ), can modify the constitution and biological function of sperm (Lane et al 2014, Schjenken et al 2020, Rimmer et al 2021.…”

“…In the male reproductive tract, EVs have been isolated from testes, epididymis, vas deferens, and accessory glands (Manin et al 1995, Sahlen et al 2010, Stewart et al 2019, Rimmer et al 2021. All these EVs contribute to the complex pool of EVs isolated from seminal plasma that is the body fluid that contains the most abundant amount of EV populations (Höög et al 2015).…”

“…All these EVs contribute to the complex pool of EVs isolated from seminal plasma that is the body fluid that contains the most abundant amount of EV populations ( Höög et al 2015 ). Some studies support the role of EVs present in the seminal plasma in assisting sperm to reach functional maturity and influence the physiology of female reproductive tract cells to support reproductive success, although their specific functions remain controversial ( Park et al 2011 , Ronquist et al 2013 , Sullivan et al 2013 , Kim et al 2015 , Machtinger et al 2016 , Murdica et al 2019 a ).…”