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Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy

Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%–30%, and 75% of these...

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Autores principales: Yaghoobi, Alireza, Nazerian, Yasaman, Meymand, Arman Zeinaddini, Ansari, Ali, Nazerian, Amirhossein, Niknejad, Hassan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871368/
https://www.ncbi.nlm.nih.gov/pubmed/36704201
http://dx.doi.org/10.3389/fcell.2022.1082657
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author Yaghoobi, Alireza
Nazerian, Yasaman
Meymand, Arman Zeinaddini
Ansari, Ali
Nazerian, Amirhossein
Niknejad, Hassan
author_facet Yaghoobi, Alireza
Nazerian, Yasaman
Meymand, Arman Zeinaddini
Ansari, Ali
Nazerian, Amirhossein
Niknejad, Hassan
author_sort Yaghoobi, Alireza
collection PubMed
description Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%–30%, and 75% of these losses are due to implantation failure (the crucial rate-limiting step of gestation). Implantation failure and abnormal placenta formation are mainly caused by defective adhesion, invasion, and angiogenesis. Placental insufficiency endangers both the mother’s and the fetus’s health. Therefore, we suggested a novel treatment strategy to improve endometrial receptivity and implantation success rate. In this strategy, regulating mir-30d expression as an upstream transcriptomic modifier of the embryo implantation results in modified expression of the involved genes in embryonic adhesion, invasion, and angiogenesis and consequently impedes implantation failure. For this purpose, “scaffold/matrix attachment regions (S/MARs)” are employed as non-viral episomal vectors, transfecting into trophoblasts by exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with a guide RNA to exclusively induce miR-30d gene expression in hypoxic stress conditions. In order to avoid concerns about the fetus’s genetic manipulation, our vector would be transfected specifically into the trophoblast layer of the blastocyst via binding to trophoblast Erb-B4 receptors without entering the inner cell mass. Additionally, S/MAR episomal vectors do not integrate with the original cell DNA. As an on/off regulatory switch, a hypoxia-sensitive promoter (HRE) is localized upstream of dCas9. The miR-30d expression increases before and during the implantation and placental insufficiency conditions and is extinguished after hypoxia elimination. This hypothesis emphasizes that improving the adhesion, invasion, and angiogenesis in the uterine microenvironment during pregnancy will result in increased implantation success and reduced placental insufficiency, as a new insight in translational medicine.
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spelling pubmed-98713682023-01-25 Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy Yaghoobi, Alireza Nazerian, Yasaman Meymand, Arman Zeinaddini Ansari, Ali Nazerian, Amirhossein Niknejad, Hassan Front Cell Dev Biol Cell and Developmental Biology Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%–30%, and 75% of these losses are due to implantation failure (the crucial rate-limiting step of gestation). Implantation failure and abnormal placenta formation are mainly caused by defective adhesion, invasion, and angiogenesis. Placental insufficiency endangers both the mother’s and the fetus’s health. Therefore, we suggested a novel treatment strategy to improve endometrial receptivity and implantation success rate. In this strategy, regulating mir-30d expression as an upstream transcriptomic modifier of the embryo implantation results in modified expression of the involved genes in embryonic adhesion, invasion, and angiogenesis and consequently impedes implantation failure. For this purpose, “scaffold/matrix attachment regions (S/MARs)” are employed as non-viral episomal vectors, transfecting into trophoblasts by exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with a guide RNA to exclusively induce miR-30d gene expression in hypoxic stress conditions. In order to avoid concerns about the fetus’s genetic manipulation, our vector would be transfected specifically into the trophoblast layer of the blastocyst via binding to trophoblast Erb-B4 receptors without entering the inner cell mass. Additionally, S/MAR episomal vectors do not integrate with the original cell DNA. As an on/off regulatory switch, a hypoxia-sensitive promoter (HRE) is localized upstream of dCas9. The miR-30d expression increases before and during the implantation and placental insufficiency conditions and is extinguished after hypoxia elimination. This hypothesis emphasizes that improving the adhesion, invasion, and angiogenesis in the uterine microenvironment during pregnancy will result in increased implantation success and reduced placental insufficiency, as a new insight in translational medicine. Frontiers Media S.A. 2023-01-10 /pmc/articles/PMC9871368/ /pubmed/36704201 http://dx.doi.org/10.3389/fcell.2022.1082657 Text en Copyright © 2023 Yaghoobi, Nazerian, Meymand, Ansari, Nazerian and Niknejad. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Yaghoobi, Alireza
Nazerian, Yasaman
Meymand, Arman Zeinaddini
Ansari, Ali
Nazerian, Amirhossein
Niknejad, Hassan
Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title_full Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title_fullStr Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title_full_unstemmed Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title_short Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
title_sort hypoxia-sensitive mirna regulation via crispr/dcas9 loaded in hybrid exosomes: a novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871368/
https://www.ncbi.nlm.nih.gov/pubmed/36704201
http://dx.doi.org/10.3389/fcell.2022.1082657
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