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Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit

The emergence of microRNA as regulators of organogenesis and tissue differentiation has stimulated interest in the ablation of microRNA expression and function during discrete periods of development. To this end, inducible, conditional modulation of microRNA expression with doxycycline-based tetracy...

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Autores principales: Hönig, Jonas, Mižíková, Ivana, Nardiello, Claudio, Surate Solaligue, David E., Daume, Maximilian J., Vadász, István, Mayer, Konstantin, Herold, Susanne, Günther, Stefan, Seeger, Werner, Morty, Rory E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959254/
https://www.ncbi.nlm.nih.gov/pubmed/29540511
http://dx.doi.org/10.1261/rna.063206.117
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author Hönig, Jonas
Mižíková, Ivana
Nardiello, Claudio
Surate Solaligue, David E.
Daume, Maximilian J.
Vadász, István
Mayer, Konstantin
Herold, Susanne
Günther, Stefan
Seeger, Werner
Morty, Rory E.
author_facet Hönig, Jonas
Mižíková, Ivana
Nardiello, Claudio
Surate Solaligue, David E.
Daume, Maximilian J.
Vadász, István
Mayer, Konstantin
Herold, Susanne
Günther, Stefan
Seeger, Werner
Morty, Rory E.
author_sort Hönig, Jonas
collection PubMed
description The emergence of microRNA as regulators of organogenesis and tissue differentiation has stimulated interest in the ablation of microRNA expression and function during discrete periods of development. To this end, inducible, conditional modulation of microRNA expression with doxycycline-based tetracycline-controlled transactivator and tamoxifen-based estrogen receptor systems has found widespread use. However, the induction agents and components of genome recombination systems negatively impact pregnancy, parturition, and postnatal development; thereby limiting the use of these technologies between late gestation and the early postnatal period. MicroRNA inhibitor (antimiR) administration also represents a means of neutralizing microRNA function in vitro and in vivo. To date, these studies have used direct (parenteral) administration of antimiRs to experimental animals. As an extension of this approach, an alternative means of regulating microRNA expression and function is described here: the maternal–placental–fetal transmission of antimiRs. When administered to pregnant dams, antimiRs were detected in offspring and resulted in a pronounced and persistent reduction in detectable steady-state free microRNA levels in the heart, kidney, liver, lungs, and brain. This effect was comparable to direct injection of newborn mouse pups with antimiRs, although maternal delivery resulted in fewer off-target effects. Furthermore, depletion of steady-state microRNA levels via the maternal route resulted in concomitant increases in steady-state levels of selected microRNA targets. This novel methodology permits the temporal regulation of microRNA function during late gestation and in neonates, without recourse to conventional approaches that rely on doxycycline and tamoxifen, which may confound studies on developmental processes.
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spelling pubmed-59592542019-06-01 Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit Hönig, Jonas Mižíková, Ivana Nardiello, Claudio Surate Solaligue, David E. Daume, Maximilian J. Vadász, István Mayer, Konstantin Herold, Susanne Günther, Stefan Seeger, Werner Morty, Rory E. RNA Method The emergence of microRNA as regulators of organogenesis and tissue differentiation has stimulated interest in the ablation of microRNA expression and function during discrete periods of development. To this end, inducible, conditional modulation of microRNA expression with doxycycline-based tetracycline-controlled transactivator and tamoxifen-based estrogen receptor systems has found widespread use. However, the induction agents and components of genome recombination systems negatively impact pregnancy, parturition, and postnatal development; thereby limiting the use of these technologies between late gestation and the early postnatal period. MicroRNA inhibitor (antimiR) administration also represents a means of neutralizing microRNA function in vitro and in vivo. To date, these studies have used direct (parenteral) administration of antimiRs to experimental animals. As an extension of this approach, an alternative means of regulating microRNA expression and function is described here: the maternal–placental–fetal transmission of antimiRs. When administered to pregnant dams, antimiRs were detected in offspring and resulted in a pronounced and persistent reduction in detectable steady-state free microRNA levels in the heart, kidney, liver, lungs, and brain. This effect was comparable to direct injection of newborn mouse pups with antimiRs, although maternal delivery resulted in fewer off-target effects. Furthermore, depletion of steady-state microRNA levels via the maternal route resulted in concomitant increases in steady-state levels of selected microRNA targets. This novel methodology permits the temporal regulation of microRNA function during late gestation and in neonates, without recourse to conventional approaches that rely on doxycycline and tamoxifen, which may confound studies on developmental processes. Cold Spring Harbor Laboratory Press 2018-06 /pmc/articles/PMC5959254/ /pubmed/29540511 http://dx.doi.org/10.1261/rna.063206.117 Text en © 2018 Hönig et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Method
Hönig, Jonas
Mižíková, Ivana
Nardiello, Claudio
Surate Solaligue, David E.
Daume, Maximilian J.
Vadász, István
Mayer, Konstantin
Herold, Susanne
Günther, Stefan
Seeger, Werner
Morty, Rory E.
Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title_full Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title_fullStr Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title_full_unstemmed Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title_short Transmission of microRNA antimiRs to mouse offspring via the maternal–placental–fetal unit
title_sort transmission of microrna antimirs to mouse offspring via the maternal–placental–fetal unit
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959254/
https://www.ncbi.nlm.nih.gov/pubmed/29540511
http://dx.doi.org/10.1261/rna.063206.117
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