1. Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse.
- Author
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Angiolini E, Sandovici I, Coan PM, Burton GJ, Sibley CP, Fowden AL, and Constância M
- Subjects
- 3-O-Methylglucose pharmacokinetics, Animals, Female, Gene Deletion, Genomic Imprinting, Inulin pharmacokinetics, Mannitol pharmacokinetics, Mice, Mice, Inbred C57BL, Nuclear Proteins metabolism, Pregnancy, beta-Alanine analogs & derivatives, beta-Alanine pharmacokinetics, Maternal-Fetal Exchange, Nuclear Proteins genetics, Placenta metabolism
- Abstract
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 solutes14 C-methyl-D-glucose and14 C-MeAIB remains unaffected at both gestational time points. However, placental passive permeability, as measured using two inert hydrophilic solutes (14 C-mannitol;14 C-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.- Published
- 2021
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