Extracellular Vesicles, the Road toward the Improvement of ART Outcomes

Abstract

Nowadays, farm animal industries use assisted reproductive technologies (ART) as a tool to manage herds’ reproductive outcomes, for a fast dissemination of genetic improvement as well as to bypass subfertility issues. ART comprise at least one of the following procedures: collection and handling of oocytes, sperm, and embryos in in vitro conditions. Therefore, in these conditions, the interaction with the oviductal environment of gametes and early embryos during fertilization and the first stages of embryo development is lost. As a result, embryos obtained in in vitro fertilization (IVF) have less quality in comparison with those obtained in vivo, and have lower chances to implant and develop into viable offspring. In addition, media currently used for IVF are very similar to those empirically developed more than five decades ago. Recently, the importance of extracellular vesicles (EVs) in the fertility process has flourished. EVs are recognized as effective intercellular vehicles for communication as they deliver their cargo of proteins, lipids, and genetic material. Thus, during their transit through the female reproductive tract both gametes, oocyte and spermatozoa (that previously encountered EVs produced by male reproductive tract) interact with EVs produced by the female reproductive tract, passing them important information that contributes to a successful fertilization and embryo development. This fact highlights that the reproductive tract EVs cargo has an important role in reproductive events, which is missing in current ART media. This review aims to recapitulate recent advances in EVs functions on the fertilization process, highlighting the latest proposals with an applied approach to enhance ART outcome through EV utilization as an additive to the media of current ART procedures.

Seminal Plasma: Relevant for Fertility?

“…Hope is now focused on the growing knowledge on EVs and their functional cargo, mostly because they would be protected by the membrane-built EVs and because they would probably be the best delivered to living spermatozoa [ 175 ]. There are several strategies, such as isolation and preservation of the EVs derived from the SP of recognized and well-documented highly fertile males, to be used as additives for improvement of fertility [ 265 ]. The rationale follows proven experiments where the SP of good freezers could improve the cryosurvival in less-good freezers [ 259 ].…”

“…Several conclusions could be made from these experiments, namely, that spermatozoa require the presence of a certain time of exposure to SP [2,260], or even a certain proportion of SP all along (often around an empirical proportion rate of 10-20% [16,22,261], in order to maintain sperm survival and fertility post AI. The moment of SP addition varied, in most instances appearing most efficient when added post-thaw [22,[261][262][263][264][265].…”

The transformative impact of extracellular vesicles on developing sperm

“…The understanding of EVs in gamete and embryo development has grown in recent years as EVs identified within follicular fluid have been shown to interact with the developing conceptus ( Gervasi et al 2020 , Han et al 2020 ). This EV-mediated process not only includes communication within the same organism but also between paternal EVs and the maternal reproductive tract ( Machtinger et al 2016 , Rodriguez-Caro et al 2019 ).…”

Small-extracellular vesicles and their microRNA cargo from porcine follicular fluids: the potential association with oocyte quality

“…The ability of EVs to modulate intercellular crosstalk is through the capacity to transfer their biomolecular cargos between different cells after being secreted in body fluids [ 5 ]. After this discovery, several studies revealed the fundamental roles of EVs in the different reproduction processes in domestic animals (reviewed by Llobat [ 6 ]) and the subsequent improvement of ART outcomes [ 7 ].…”