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

Abstract

Recently, many studies have investigated the role of extracellular vesicles (EVs) on reproductive events, including embryo development and death, oviduct–embryo crosstalk, in vitro fertilization and others. The aim of this study was to demonstrate whether outgrowth embryo–derived EVs function as bioactive molecules and regulate mouse embryonic developmental competence in vitro and implantation potential in utero. The EVs from mouse outgrowth embryos on 7.5 days postcoitum were detected and selectively isolated to evaluate the embryotrophic functions on preimplantation embryos. Developmental outcomes such as the percentage of blastocyst formation, hatching, and trophoblastic outgrowth were assessed. Furthermore, the total cell number and apoptotic index of blastocysts, which were incubated with EVs during the culture period, were evaluated by fluorescence microscopy. Implantation potential in utero was investigated following embryo transfer. The EVs from outgrowth embryo–conditioned media have rounded membrane structures that range in diameter from 20 to 225 nm. Incubation with EVs improved preimplantation embryonic development by increasing cell proliferation and decreasing apoptosis in blastocysts. Moreover, the implantation rates following embryo transfer were significantly higher in EV–supplemented embryos compared with the control. Collectively, EVs from outgrowth embryo could enhance the embryonic developmental competence and even implantation potential in mice.

Embryonic extracellular vesicles as informers to the immune cells at the maternal–fetal interface

“…The presence of the EVs has been demonstrated in the embryo culture medium from different species, such as bovines [28], porcines [29], mice [30] and humans [7]. The diameter of EVs found in the embryo spent media is quite different among these species, as shown in Table 1.…”

Extracellular Vesicles Function as Bioactive Molecular Transmitters in the Mammalian Oviduct: An Inspiration for Optimizing in Vitro Culture Systems and Improving Delivery of Exogenous Nucleic Acids during Preimplantation Embryonic Development

“…In pigs, the presence of early embryos regulates the expression of Ticam2, an immune-related gene, in the oviduct epithelium, which depends on the embryo developmental stages [71]. Moreover, early embryos can also release EVs [74][75][76][77] that in turn might be components of OVS. Given this background, we hypothesized that oviduct may also respond to preimplantation embryos due to embryo-derived EVs.…”

Identification and Characterization of Extracellular Vesicles and Its DNA Cargo Secreted During Murine Embryo Development

“…The production and secretion of EVs by the embryo have been reported in different species from bovine [39], pig [40], mouse [41], and human [3]. Although different size ranges have been demonstrated among species, all shared phenotypic markers such as CD63 and CD9 [42].…”