Porcine oviductal extracellular vesicles facilitate early embryonic development via relief of endoplasmic reticulum stress

Abstract

The key to successful in vitro embryo production (IVEP) is to mimic the natural in vivo oviductal microenvironment. Although the chemically defined media in extensive use for the in vitro culture of mammalian embryos is based on the composition of oviductal fluid, the IVEP systems in current use must still bypass the oviduct to produce embryos in vitro. Extracellular vesicles (EVs) in the oviduct are versatile intercellular delivery vehicles for maternal–embryo communication, and a lack of them can be associated with failed early embryonic development under in vitro culture conditions. Herein, we isolated EVs from porcine oviduct fluid and confirmed that oviductal EV supplementation improves the embryonic development of parthenogenetically activated (PA) embryos in terms of blastocyst formation rates and total cell numbers. Our experiments also revealed that a beneficial effect of oviductal EVs on PA embryos was achievable, at least in part, by relieving endoplasmic reticulum stress. These results suggest that the maternal–embryo communication mediated by oviductal EVs benefits early embryonic development. Given the contribution of oviductal EVs to early embryonic development, these findings offer novel insights for the optimization of current IVEP systems.

Protein Disulfide Isomerase-Enriched Extracellular Vesicles from Bladder Cancer Cells Support Tumor Survival and Malignant Transformation in the Bladder

“…We found that under ER stress, BC cells released high levels of oxidized PDI within EVs, thereby mitigating the ROS production and consequent cell death, ultimately promoting BC cell survival. This nding is highly innovative and aligns well with the observation that, while cells continuously shed EVs at steady state, multivesicular body formation and EV release are enhanced under conditions of ER stress or oxidative stress (44,45), supporting this process of EV-mediated oxidized PDI export as a stress relief mechanism (34).…”

“…This, coupled with the potential need for tumor cells to regulate PDI activity and attendant oxidative stress within a tolerable range conducive to proliferation and drug resistance, raises the possibility that EVs may provide a release valve to manage levels of intracellular stress. Indeed, EVmediated relief of excessive ER stress has been proposed in developmental settings (34), and may be co-opted by tumor cells, indirectly exposing non-malignant recipient cells to this stress in the process.…”

Uterine Fluid Extracellular Vesicles Proteome Is Altered During the Estrous Cycle

“…In the current study, UF-EVs were supplemented to the embryo culture media, which showed significantly improved blastocyst development rates compared to nontreated control. Previous studies have shown that EVs are internalized by embryos ( 26 , 57 ) being able to reduce ROS levels in embryos ( 58 ), which improves blastocyst rates. However, our finding needs further investigation to understand the differences in anti-oxidation–protective effects on embryos, which are supplemented directly to culture medium compared to antioxidants that are carried by EVs.…”

“…Embryo-maternal communication and signaling between endometrial cells during pre-implantation period is crucial in mediating embryo and endometrial growth, which both is needed for successful pregnancy. There are plethora of evidence supporting the involvement of EVs from either side in maternal-embryo cross talks in establishment of pregnancy and development of the embryo beyond the implantation ( 14 , 24 , 26 , 27 ). However, the optimal bovine UF-EV protein composition leading to successful pregnancy is yet to be established.…”

Messenger roles of extracellular vesicles during fertilization of gametes, development and implantation: Recent advances

“…Porcine O-EVs can decrease caspase-3 gene expression, decrease blastocyst cell apoptosis, and increase blastocyst formation rate. This could be caused by lowering the expression of the sXBP1, ATF4, and GRP78 genes in order to reduce embryonic ER stress ( Fu et al, 2022 ). Furthermore, O-EVs have an energy regulation effect on embryo development.…”