Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI

Abstract Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. Th...

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Autores principales:	Philipp Boehm-Sturm, Susanne Mueller, Nancy Freitag, Sophia Borowski, Marco Foddis, Stefan P. Koch, Sebastian Temme, Ulrich Flögel, Sandra M. Blois
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b1ff34c47de43fcb4f16e9a1d0714ed
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spelling	oai:doaj.org-article:2b1ff34c47de43fcb4f16e9a1d0714ed2021-12-02T15:23:28ZPhenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI10.1038/s41598-020-80408-92045-2322https://doaj.org/article/2b1ff34c47de43fcb4f16e9a1d0714ed2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80408-9https://doaj.org/toc/2045-2322Abstract Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. The goal of this exploratory study was to establish a technique to noninvasively characterize placental partial pressure of oxygen (PO2) in vivo in the Lgals1 (lectin, galactoside-binding, soluble, 1) deficient mouse model of preeclampsia using fluorine magnetic resonance imaging. We hypothesized a decrease in placental oxygenation in knockout mice. Wildtype and knockout animals received fluorescently labeled perfluoro-5-crown-15-ether nanoemulsion i.v. on day E14-15 during pregnancy. Placental PO2 was assessed via calibrated 19F MRI saturation recovery T1 mapping. A gas challenge with varying levels of oxygen in breathing air (30%, 60% and 100% O2) was used to validate that changes in oxygenation can be detected in freely breathing, anesthetized animals. At the end of the experiment, fluorophore-coupled lectin was injected i.v. to label the vasculature for histology. Differences in PO2 between breathing conditions and genotype were statistically analyzed with linear mixed-effects modeling. As expected, a significant increase in PO2 with increasing oxygen in breathing air was found. PO2 in Lgals1 knockout animals was decreased but this effect was only present at 30% oxygen in breathing air, not at 60% and 100%. Histological examinations showed crossing of the perfluorocarbon nanoemulsion to the fetal blood pool but the dominating contribution of 19F MR signal is estimated at > 70% from maternal plasma based on volume fraction measurements of previous studies. These results show for the first time that 19F MRI can characterize oxygenation in mouse models of placental malfunction.Philipp Boehm-SturmSusanne MuellerNancy FreitagSophia BorowskiMarco FoddisStefan P. KochSebastian TemmeUlrich FlögelSandra M. BloisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philipp Boehm-Sturm Susanne Mueller Nancy Freitag Sophia Borowski Marco Foddis Stefan P. Koch Sebastian Temme Ulrich Flögel Sandra M. Blois Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
description	Abstract Placental hypoperfusion and hypoxia are key drivers in complications during fetal development such as fetal growth restriction and preeclampsia. In order to study the mechanisms of disease in mouse models, the development of quantitative biomarkers of placental hypoxia is a prerequisite. The goal of this exploratory study was to establish a technique to noninvasively characterize placental partial pressure of oxygen (PO2) in vivo in the Lgals1 (lectin, galactoside-binding, soluble, 1) deficient mouse model of preeclampsia using fluorine magnetic resonance imaging. We hypothesized a decrease in placental oxygenation in knockout mice. Wildtype and knockout animals received fluorescently labeled perfluoro-5-crown-15-ether nanoemulsion i.v. on day E14-15 during pregnancy. Placental PO2 was assessed via calibrated 19F MRI saturation recovery T1 mapping. A gas challenge with varying levels of oxygen in breathing air (30%, 60% and 100% O2) was used to validate that changes in oxygenation can be detected in freely breathing, anesthetized animals. At the end of the experiment, fluorophore-coupled lectin was injected i.v. to label the vasculature for histology. Differences in PO2 between breathing conditions and genotype were statistically analyzed with linear mixed-effects modeling. As expected, a significant increase in PO2 with increasing oxygen in breathing air was found. PO2 in Lgals1 knockout animals was decreased but this effect was only present at 30% oxygen in breathing air, not at 60% and 100%. Histological examinations showed crossing of the perfluorocarbon nanoemulsion to the fetal blood pool but the dominating contribution of 19F MR signal is estimated at > 70% from maternal plasma based on volume fraction measurements of previous studies. These results show for the first time that 19F MRI can characterize oxygenation in mouse models of placental malfunction.
format	article
author	Philipp Boehm-Sturm Susanne Mueller Nancy Freitag Sophia Borowski Marco Foddis Stefan P. Koch Sebastian Temme Ulrich Flögel Sandra M. Blois
author_facet	Philipp Boehm-Sturm Susanne Mueller Nancy Freitag Sophia Borowski Marco Foddis Stefan P. Koch Sebastian Temme Ulrich Flögel Sandra M. Blois
author_sort	Philipp Boehm-Sturm
title	Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
title_short	Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
title_full	Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
title_fullStr	Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
title_full_unstemmed	Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI
title_sort	phenotyping placental oxygenation in lgals1 deficient mice using 19f mri
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2b1ff34c47de43fcb4f16e9a1d0714ed
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Phenotyping placental oxygenation in Lgals1 deficient mice using 19F MRI

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