The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms - PubMed (original) (raw)
. 2025 Jan 9:S1534-5807(24)00776-7.
doi: 10.1016/j.devcel.2024.12.037. Online ahead of print.
Affiliations
- PMID: 39814015
- DOI: 10.1016/j.devcel.2024.12.037
Free article
The spatial zonation of the murine placental vasculature is specified by epigenetic mechanisms
Stephanie Gehrs et al. Dev Cell. 2025.
Free article
Abstract
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.
Keywords: DNA methylation; DNMT3A; angiogenesis; epigenetic regulation; growth retardation; placental endothelium; spatial zonation.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The other authors declare no competing interests.
Similar articles
- Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India.
Sundrani D, Kapare A, Yadav H, Randhir K, Gupte S, Joshi S. Sundrani D, et al. Epigenomics. 2025 Jan;17(1):21-31. doi: 10.1080/17501911.2024.2438593. Epub 2024 Dec 10. Epigenomics. 2025. PMID: 39655657 - Depressing time: Waiting, melancholia, and the psychoanalytic practice of care.
Salisbury L, Baraitser L. Salisbury L, et al. In: Kirtsoglou E, Simpson B, editors. The Time of Anthropology: Studies of Contemporary Chronopolitics. Abingdon: Routledge; 2020. Chapter 5. In: Kirtsoglou E, Simpson B, editors. The Time of Anthropology: Studies of Contemporary Chronopolitics. Abingdon: Routledge; 2020. Chapter 5. PMID: 36137063 Free Books & Documents. Review. - Radiation Effects On The Fetus.
Kumar R, De Jesus O. Kumar R, et al. 2023 Aug 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. 2023 Aug 23. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 33232028 Free Books & Documents. - Maternal-fetal interfaces transcriptome changes associated with placental insufficiency and a novel gene therapy intervention.
Jones HN, Davenport BN, Wilson RL. Jones HN, et al. Physiol Genomics. 2025 Jan 1;57(1):8-15. doi: 10.1152/physiolgenomics.00131.2024. Epub 2024 Oct 7. Physiol Genomics. 2025. PMID: 39374081 - Single Large-Scale Mitochondrial DNA Deletion Syndromes.
Goldstein A, Falk MJ. Goldstein A, et al. 2003 Dec 17 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2003 Dec 17 [updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301382 Free Books & Documents. Review.
LinkOut - more resources
Full Text Sources
Miscellaneous