Oviduct extracellular vesicles protein content and their role during oviduct–embryo cross-talk

Abstract

Successful pregnancy requires an appropriate communication between the mother and the embryo. Recently, exosomes and microvesicles, both membrane-bound extracellular vesicles (EVs) present in the oviduct fluid have been proposed as key modulators of this unique cross-talk. However, little is known about their content and their role during oviduct-embryo dialog. Given the known differences in secretions by and oviduct epithelial cells (OEC), we aimed at deciphering the oviduct EVs protein content from both sources. Moreover, we analyzed their functional effect on embryo development. Our study demonstrated for the first time the substantial differences between and oviduct EVs secretion/content. Mass spectrometry analysis identified 319 proteins in EVs, from which 186 were differentially expressed when and EVs were compared ( < 0.01). Interestingly, 97 were exclusively expressed in EVs, 47 were present only in and 175 were common. Functional analysis revealed key proteins involved in sperm-oocyte binding, fertilization and embryo development, some of them lacking in EVs. Moreover, we showed that-produced embryos were able to internalize EVs during culture with a functional effect in the embryo development. EVs increased blastocyst rate, extended embryo survival over time and improved embryo quality. Our study provides the first characterization of oviduct EVs, increasing our understanding of the role of oviduct EVs as modulators of gamete/embryo-oviduct interactions. Moreover, our results point them as promising tools to improve embryo development and survival under conditions.

Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5‐methylcytosine

“…Notably, oviduct fluid‐derived EVs decreased ROS, 5‐mC, DNMT1, and DNMT3a levels and increased the blastocyst rate of embryos in the in vitro experiments. This is in line with a previous study where EVs derived from bovine oviduct fluid were found crucial to fertilization and early‐stage embryonic development . Moreover, this beneficial effect of EVs was attenuated by luzindole in our study, indicating a positive association between melatonin and EVs on ROS and 5‐mC levels.…”

“…EVs consist of lipids, proteins, RNA, and other components . EV lipidomic studies characterized EV lipid species from reticulocytes, B lymphocytes, mast cells, dendritic cells, and prostate cancer cells, and approximately 280 molecular lipid species were characterized from prostate cancer cellline‐derived EVs, while 319 proteins were identified in EVs, some of which may bind to melatonin, such as albumin, and pepsin . Melatonin can interact with hydrophobic sites due to its lipid solubility .…”

“…Extracellular vesicles (EVs) have been reported to mediate intercellular interactions by transferring noncoding RNAs and proteins . Furthermore, oviductal EVs play an important role in oviduct–embryo interactions . Although, melatonin and EVs play important roles in reproduction, the melatonin and EV‐based communication is absent in embryo culture in vitro.…”

Extracellular vesicles from oviductal isthmus and ampulla stimulate the induced acrosome reaction and signaling events associated with capacitation in bovine spermatozoa

“…The consequences of such differences are not known, but it is worth noting that EV from ampulla may be involved in the fine tuning sperm performance in the proximity of the egg. Consistently, oviductal EV may also modulate embryo physiology …”

Embryotrophic effects of extracellular vesicles derived from outgrowth embryos in pre‐ and peri‐implantation embryonic development in mice

“…Interestingly, our data showed that EVs derived from outgrowth have unidentified proteins and genetic materials, and it also proved EVs are known to transfer various biomolecules, including proteins, lipids, mRNAs, and miRNAs (Thery et al, ). Alminana et al () reported that coincubation with bovine oviduct EVs improved blastocyst rates, hatching ability, and blastomere count of the blastocyst. Protein contents in oviduct EVs cargo may influence embryonic development and quality by activation of gamete interaction.…”