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The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms

The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled...

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Main Authors: Gehrs, Stephanie (Author) , Jakab, Moritz (Author) , Gutjahr, Ewgenija (Author) , Gu, Zuguang (Author) , Weichenhan, Dieter (Author) , Mallm, Jan-Philipp (Author) , Mogler, Carolin (Author) , Schlesner, Matthias (Author) , Plass, Christoph (Author) , Schlereth, Katharina (Author) , Augustin, Hellmut (Author)
Format: Article (Journal)
Language:English
Published: 14 January 2025
In: Developmental cell
Year: 2025, Volume: 60, Issue: 10, Pages: 1467-1482, e8
ISSN:1878-1551
DOI:10.1016/j.devcel.2024.12.037
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.devcel.2024.12.037
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1534580724007767
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Author Notes:Stephanie Gehrs, Moritz Jakab, Ewgenija Gutjahr, Zuguang Gu, Dieter Weichenhan, Jan-Philipp Mallm, Carolin Mogler, Matthias Schlesner, Christoph Plass, Katharina Schlereth, Hellmut G. Augustin
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Summary:The labyrinthian fetoplacental capillary network is vital for proper nourishment of the developing embryo. Dysfunction of the maternal-fetal circulation is a primary cause of placental insufficiency. Here, we show that the spatial zonation of the murine placental labyrinth vasculature is controlled by flow-regulated epigenetic mechanisms. Spatiotemporal transcriptomic profiling identified a gradual change in the expression of epigenetic enzymes, including the de novo DNA methyltransferase 3a (DNMT3A). Loss of Dnmt3a resulted in DNA hypomethylation and perturbation of zonated placental gene expression. The resulting global DNA hypomethylation impaired the angiogenic capacity of endothelial cells. Global or endothelium-predominant deletion of Dnmt3a resulted in impaired placental vascularization and fetal growth retardation (FGR). Human placental endothelial gene expression profiling associated preeclampsia with reduced DNMT3A expression. Collectively, our study identified DMNT3A as critical methylome-regulator of placental endothelial gene expression and function with clinical implications for placental dysfunction, as it occurs during preeclampsia or FGR.
Item Description:Artikelversion: 19. Mai 2025
Gesehen am 08.09.2025
Physical Description:Online Resource
ISSN:1878-1551
DOI:10.1016/j.devcel.2024.12.037

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