Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse
Fowden, Abigail L.
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Angiolini, E., Sandovici, I., Coan, P. M., Burton, G. J., Sibley, C. P., Fowden, A. L., & Constância, M. (2021). Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse. Genes, 12 (5)https://doi.org/10.3390/genes12050639
Genomic imprinting, an epigenetic phenomenon that causes the expression of a small set of genes in a parent-of-origin-specific manner, is thought to have co-evolved with placentation. Many imprinted genes are expressed in the placenta, where they play diverse roles related to development and nutrient supply function. However, only a small number of imprinted genes have been functionally tested for a role in nutrient transfer capacity in relation to the structural characteristics of the exchange labyrinthine zone. Here, we examine the transfer capacity in a mouse model deficient for the maternally expressed Phlda2 gene, which results in placental overgrowth and a transient reduction in fetal growth. Using stereology, we show that the morphology of the labyrinthine zone in Phlda2−/+ mutants is normal at E16 and E19. In vivo placental transfer of radiolabeled solutes 14C-methyl-D-glucose and 14C-MeAIB remains unaffected at both gestational time points. However, placental passive permeability, as measured using two inert hydrophilic solutes (14C-mannitol; 14C-inulin), is significantly higher in mutants. Importantly, this increase in passive permeability is associated with fetal catch-up growth. Our findings uncover a key role played by the imprinted Phlda2 gene in modifying placental passive permeability that may be important for determining fetal growth.
Phlda2, genomic imprinting, placenta, fetal growth, passive permeability
Biotechnology and Biological Sciences Research Council (BB/B50118X/1)
EU-FP6 Epigenome Network of Excellence (503433)
External DOI: https://doi.org/10.3390/genes12050639
This record's URL: https://www.repository.cam.ac.uk/handle/1810/321584