Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse.

Emily Angiolini,Ionel Sandovici,Graham J Burton,Abigail L Fowden,Miguel Constância,Philip M Coan,Colin P Sibley

doi:10.3390/genes12050639

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 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.

Highlights

Genomic imprinting is an epigenetic phenomenon that leads to allele-specific expression depending on the parent-of-origin of the allele [1]
Mutant placentae were on average ~129% of Phlda2+/+ littermates at both E16 and E19 of gestation (Table 1) (p < 0.001), whereas there was a modest but significant reduction in fetal weight to 96% at E16 (p < 0.05), which was lost by E19 (99%, p = NS, not significant)
In this study, we filled an important gap in our knowledge about the role played by the imprinted Phlda2 gene in the placenta

Summary

Introduction

Genomic imprinting is an epigenetic phenomenon that leads to allele-specific expression depending on the parent-of-origin of the allele [1]. There is an evolutionary link between genomic imprinting and placentation, strongly supporting the hypothesis that imprinted genes play key roles in allocation of maternal resources via the placenta. Reinforcing the notion that imprinted genes have a special role in placental biology, a large proportion of the approximately 100 imprinted genes identified to date in mice and humans are highly expressed in the placenta [3]. Mouse models of loss-of-imprinting, leading to either reactivation of the silent allele or silencing of the active allele, have uncovered a number of placental phenotypes, ranging from abnormal growth and structure to changes in placental transfer capacity and endocrine function (reviewed by [4,5,6]).

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