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Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts

Extracellular vesicles (EVs) and their cargo microRNAs (miRNAs) are important regulators of embryo development to the blastocyst stage and beyond. Before implantation can take place, hatching of blastocysts from their zona pellucida is required. However, underlying mechanisms by which blastocyst for...

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Autores principales: Pavani, Krishna Chaitanya, Meese, Tim, Pascottini, Osvaldo Bogado, Guan, XueFeng, Lin, Xiaoyuan, Peelman, Luc, Hamacher, Joachim, Van Nieuwerburgh, Filip, Deforce, Dieter, Boel, Annekatrien, Heindryckx, Björn, Tilleman, Kelly, Van Soom, Ann, Gadella, Bart M., Hendrix, An, Smits, Katrien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944274/
https://www.ncbi.nlm.nih.gov/pubmed/35298333
http://dx.doi.org/10.1073/pnas.2122708119
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author Pavani, Krishna Chaitanya
Meese, Tim
Pascottini, Osvaldo Bogado
Guan, XueFeng
Lin, Xiaoyuan
Peelman, Luc
Hamacher, Joachim
Van Nieuwerburgh, Filip
Deforce, Dieter
Boel, Annekatrien
Heindryckx, Björn
Tilleman, Kelly
Van Soom, Ann
Gadella, Bart M.
Hendrix, An
Smits, Katrien
author_facet Pavani, Krishna Chaitanya
Meese, Tim
Pascottini, Osvaldo Bogado
Guan, XueFeng
Lin, Xiaoyuan
Peelman, Luc
Hamacher, Joachim
Van Nieuwerburgh, Filip
Deforce, Dieter
Boel, Annekatrien
Heindryckx, Björn
Tilleman, Kelly
Van Soom, Ann
Gadella, Bart M.
Hendrix, An
Smits, Katrien
author_sort Pavani, Krishna Chaitanya
collection PubMed
description Extracellular vesicles (EVs) and their cargo microRNAs (miRNAs) are important regulators of embryo development to the blastocyst stage and beyond. Before implantation can take place, hatching of blastocysts from their zona pellucida is required. However, underlying mechanisms by which blastocyst formation and hatching are initiated remain largely unknown. Here, we provide evidence that embryonic EVs containing bta-miR-378a-3p play a crucial role in blastocyst hatching, using a bovine model. A customized procedure was used to isolate EV-miRNAs from culture droplets conditioned by individual bovine embryos that either developed to the blastocyst stage or did not (nonblastocyst). RNA sequencing identified 69 differentially expressed miRNAs between EVs derived from blastocyst conditioned medium (CM) and nonblastocyst CM. Among the miRNAs up-regulated in blastocyst CM, we selected bta-miR-378a-3p for further validation by functionality testing on developing in vitro embryos by means of mimics and inhibitors. Supplementing the embryo culture medium with miR-378a-3p mimic significantly improved blastocyst quality, with higher cell numbers and reduced apoptosis, and improved hatching, while the opposite was found after supplementation with miR-378a-3p inhibitor (P < 0.01). Transcriptomic analysis of embryos treated with miR-378 mimic/inhibitor showed differential expression (P < 0.01) of genes associated with embryo development and implantation, including RAP1GAP, ARFGEF2, SLC7A6, CENPA, SP1, LDLR, PYCR1, MYD88, TPP1, and NCOA3. In conclusion, miR-378a-3p is up-regulated in EVs secreted by embryos that develop to the blastocyst stage, and this EV-derived miR-378a-3p increases blastocyst quality and regulates embryo hatching, which is essential for embryo implantation.
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spelling pubmed-89442742022-03-25 Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts Pavani, Krishna Chaitanya Meese, Tim Pascottini, Osvaldo Bogado Guan, XueFeng Lin, Xiaoyuan Peelman, Luc Hamacher, Joachim Van Nieuwerburgh, Filip Deforce, Dieter Boel, Annekatrien Heindryckx, Björn Tilleman, Kelly Van Soom, Ann Gadella, Bart M. Hendrix, An Smits, Katrien Proc Natl Acad Sci U S A Biological Sciences Extracellular vesicles (EVs) and their cargo microRNAs (miRNAs) are important regulators of embryo development to the blastocyst stage and beyond. Before implantation can take place, hatching of blastocysts from their zona pellucida is required. However, underlying mechanisms by which blastocyst formation and hatching are initiated remain largely unknown. Here, we provide evidence that embryonic EVs containing bta-miR-378a-3p play a crucial role in blastocyst hatching, using a bovine model. A customized procedure was used to isolate EV-miRNAs from culture droplets conditioned by individual bovine embryos that either developed to the blastocyst stage or did not (nonblastocyst). RNA sequencing identified 69 differentially expressed miRNAs between EVs derived from blastocyst conditioned medium (CM) and nonblastocyst CM. Among the miRNAs up-regulated in blastocyst CM, we selected bta-miR-378a-3p for further validation by functionality testing on developing in vitro embryos by means of mimics and inhibitors. Supplementing the embryo culture medium with miR-378a-3p mimic significantly improved blastocyst quality, with higher cell numbers and reduced apoptosis, and improved hatching, while the opposite was found after supplementation with miR-378a-3p inhibitor (P < 0.01). Transcriptomic analysis of embryos treated with miR-378 mimic/inhibitor showed differential expression (P < 0.01) of genes associated with embryo development and implantation, including RAP1GAP, ARFGEF2, SLC7A6, CENPA, SP1, LDLR, PYCR1, MYD88, TPP1, and NCOA3. In conclusion, miR-378a-3p is up-regulated in EVs secreted by embryos that develop to the blastocyst stage, and this EV-derived miR-378a-3p increases blastocyst quality and regulates embryo hatching, which is essential for embryo implantation. National Academy of Sciences 2022-03-17 2022-03-22 /pmc/articles/PMC8944274/ /pubmed/35298333 http://dx.doi.org/10.1073/pnas.2122708119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Pavani, Krishna Chaitanya
Meese, Tim
Pascottini, Osvaldo Bogado
Guan, XueFeng
Lin, Xiaoyuan
Peelman, Luc
Hamacher, Joachim
Van Nieuwerburgh, Filip
Deforce, Dieter
Boel, Annekatrien
Heindryckx, Björn
Tilleman, Kelly
Van Soom, Ann
Gadella, Bart M.
Hendrix, An
Smits, Katrien
Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title_full Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title_fullStr Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title_full_unstemmed Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title_short Hatching is modulated by microRNA-378a-3p derived from extracellular vesicles secreted by blastocysts
title_sort hatching is modulated by microrna-378a-3p derived from extracellular vesicles secreted by blastocysts
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944274/
https://www.ncbi.nlm.nih.gov/pubmed/35298333
http://dx.doi.org/10.1073/pnas.2122708119
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