The theranostic roles of extracellular vesicles in pregnancy disorders

Saadeldin, Islam M.; Tanga, Bereket Molla; Bang, Seonggyu; Fang, Xun; Yoon, Ki-young; Lee, Sanghoon; Cho, Jongki

doi:10.12750/jarb.37.1.2

Cited by 9 publications

(3 citation statements)

References 106 publications

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“…At the same time, we found that OEC EVs could promote the expression of TEAD4 and CDX2. TEAD4 and CDX2 are important regulatory genes in early embryos that can promote the differentiation of trophoblast cell lineages [45][46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Oviduct Epithelial Cell-Derived Extracellular Vesicles Improve Porcine Trophoblast Outgrowth

Fang

Tanga

Bang

et al. 2022

Veterinary Sciences

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Porcine species have a great impact on studies on biomaterial production, organ transplantation and the development of biomedical models. The low efficiency of in vitro-produced embryos to derive embryonic stem cells has made achieving this goal a challenge. The fallopian tube plays an important role in the development of embryos. Extracellular vesicles (EVs) secreted by oviductal epithelial cells play an important role in the epigenetic regulation of embryo development. We used artificially isolated oviductal epithelial cells and EVs. In this study, oviductal epithelial cell (OEC) EVs were isolated and characterized through transmission electron microscopy, nanoparticles tracking analysis, western blotting and proteomics. We found that embryo development and blastocyst formation rate was significantly increased (14.3% ± 0.6% vs. 6.0% ± 0.6%) after OEC EVs treatment. According to our data, the inner cell mass (ICM)/trophectoderm (TE) ratio of the embryonic cell number increased significantly after OEC EVs treatment (43.7% ± 2.3% vs. 28.4% ± 2.1%). Meanwhile, the attachment ability of embryos treated with OEV EVs was significantly improved (43.5% ± 2.1% vs. 29.2% ± 2.5%, respectively). Using quantitative polymerase chain reaction (qPCR), we found that the expression of reprogramming genes (POU5F1, SOX2, NANOG, KLF4 and c-Myc) and implantation-related genes (VIM, KRT8, TEAD4 and CDX2) significantly increased in OEC EV-treated embryos. We report that OEC EV treatment can improve the development and implantation abilities of embryos.

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Section: Discussionmentioning

confidence: 99%

Oviduct Epithelial Cell-Derived Extracellular Vesicles Improve Porcine Trophoblast Outgrowth

Fang

Tanga

Bang

et al. 2022

Veterinary Sciences

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“…Extracellular vesicles (EVs) are nanovesicles enclosed by a lipid bilayer and can be released from all living cells [9]. They contain many biologically active molecular substances such as proteins, mRNAs and miRNAs, which play active roles in regulating different physiological events [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of follicular fluid-derived extracellular vesicles improve in vitro maturation and embryonic development of porcine oocytes

Kang,

Bang,

Kim

et al. 2023

Korean J Vet Res

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To optimize the most efficient method for porcine in vitro maturation (IVM), we compared the effects of supplementing extracellular vesicles (EVs) derived from porcine follicular fluid (pFF). The cumulus oocyte complexes were grouped into 4 groups with different supplementations as following: pFF (G1), pFF-depleted EVs (G2), EVs (G3) and control (G4) groups. After IVM with different supplementations, maturation rates and the developmental competences of porcine oocytes and blastocyst development were investigated. Additionally, glutathione (GSH) and reactive oxygen species (ROS) levels were measured in mature oocytes. The EVs were isolated and characterized with cryo-TEM and nanoparticle tracking analysis. The pFF significantly affected the maturation rate, whereas the presence of EVs did not show notable difference in the maturation rates. Although there were numerical increases in the measured parameters in EV and pFF-depleted EVs groups, no significant differences were observed between them. The EV group showed similar oocyte maturation rate for both positive and negative control groups. The GSH was not different among the groups, but ROS levels were significantly lower in pFF-supplemented group when compared with other groups with the highest level in the control group. G2 group wasn’t significantly different G1 and G3 group. G3 group wasn’t significantly different from G2 and G4 group. This suggests that EVs in IVM medium which probably effected partially to protect against oxidative stress and potentially enhance the quality of oocytes. This study indicates that the EVs in pFF play a significant role in improving the efficiency of oocyte maturation in porcine.

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“…For instance, the endogenous factors are formed or released by the embryos themselves, while the exogenous factors are released by the maternal cells and hamper the developmental competence such as miRNAs. Several cargos of protein, mRNA, miRNA, and metabolites are carried through the extracellular vesicles (EVs) and affect the growth of the embryo [4,8,9]. Moreover, the interplay between the EVs derived from the endometrium during embryo implantation in humans and animals has been investigated [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

Saadeldin

Tanga

Bang

et al. 2022

Cells

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Extracellular vesicles (EVs) are nanosized vesicles that act as snapshots of cellular components and mediate cellular communications, but they may contain cargo contents with undesired effects. We developed a model to improve the effects of endometrium-derived EVs (Endo-EVs) on the porcine embryo attachment in feeder-free culture conditions. Endo-EVs cargo contents were analyzed using conventional and real-time PCR for micro-RNAs, messenger RNAs, and proteomics. Porcine embryos were generated by parthenogenetic electric activation in feeder-free culture conditions supplemented with or without Endo-EVs. The cellular uptake of Endo-EVs was confirmed using the lipophilic dye PKH26. Endo-EVs cargo contained miR-100, miR-132, and miR-155, together with the mRNAs of porcine endogenous retrovirus (PERV) and β-catenin. Targeting PERV with CRISPR/Cas9 resulted in reduced expression of PERV mRNA transcripts and increased miR-155 in the Endo-EVs, and supplementing these in embryos reduced embryo attachment. Supplementing the medium containing Endo-EVs with miR-155 inhibitor significantly improved the embryo attachment with a few outgrowths, while supplementing with Rho-kinase inhibitor (RI, Y-27632) dramatically improved both embryo attachment and outgrowths. Moreover, the expression of miR-100, miR-132, and the mRNA transcripts of BCL2, zinc finger E-box-binding homeobox 1, β-catenin, interferon-γ, protein tyrosine phosphatase non-receptor type 1, PERV, and cyclin-dependent kinase 2 were all increased in embryos supplemented with Endo-EVs + RI compared to those in the control group. Endo-EVs + RI reduced apoptosis and increased the expression of OCT4 and CDX2 and the cell number of embryonic outgrowths. We examined the individual and combined effects of RI compared to those of the miR-155 mimic and found that RI can alleviate the negative effects of the miR-155 mimic on embryo attachment and outgrowths. EVs can improve embryo attachment and the unwanted effects of the de trop cargo contents (miR-155) can be alleviated through anti-apoptotic molecules such as the ROCK inhibitor.

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The theranostic roles of extracellular vesicles in pregnancy disorders

Cited by 9 publications

References 106 publications

Oviduct Epithelial Cell-Derived Extracellular Vesicles Improve Porcine Trophoblast Outgrowth

Oviduct Epithelial Cell-Derived Extracellular Vesicles Improve Porcine Trophoblast Outgrowth

Effects of follicular fluid-derived extracellular vesicles improve in vitro maturation and embryonic development of porcine oocytes

ROCK Inhibitor (Y-27632) Abolishes the Negative Impacts of miR-155 in the Endometrium-Derived Extracellular Vesicles and Supports Embryo Attachment

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