Extracellular vesicles in seminal plasma : A safe and relevant tool to improve fertility in livestock?

Seminal plasma (SP) is not a pre-requisite for pregnancy. Yet, this heterogeneous, composite SP has proven relevant for fertility, as mediator for cell-to-cell communication between producing cells, spermatozoa and the female internal genital tract, regulating complex reproductive pro-cesses. Bearing hormones, proteins, cytokines as well as nuclei acids in nano-sized lipid bilayer seminal extracellular vesicles (sEVs), the SP concerts signaling to the female. Signals influence timing of ovulation, sperm transport and, particularly, enable the female immune system to balance her cryptic choice to engage into pregnancy or reject an eventual fertilization. This essay, focusing on livestock in general and pigs in particular, discusses the intrinsic roles of sEVs with regards to reproductive homeostasis, while binding and internalizing their cargo in spermatozoa and female tract epithelia to regulate their functional activity. Since prior studies had inconclu-sive results using bulk SP or single SP-contained free molecules, argumentation is hereby pro-vided to increase the current incipient research on livestock sEVs, where fragile molecules relevant for fertility are shielded from degradation during handling. Seminal EVs isolated from SP can be used for andrological diagnosis and perhaps to select breeders with optimal fertility. Moreover, sEVs can be laboratory-uploaded with specific molecules or even engineered as lipid nanodroplets used as additives for extenders to improve fertility after artificial insemination (AI) or reproductive biotechnologies.Funding Agencies|Research Council FORMAS, Stockholm [2019-00288]; Spanish Ministry of Science and Innovation, Madrid, Spain [MCIN/AEI/10.13039/501100011033, PID2020-113493RB-I00]