Placental-specific IGF-II is a major modulator of placental and fetal growth

Miguel Constância (), Myriam Hemberger, Jennifer Hughes, Wendy Dean, Anne Ferguson-Smith, Reinald Fundele, Francesca Stewart, Gavin Kelsey, Abigail Fowden, Colin Sibley and Wolf Reik ()
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Miguel Constância: The Babraham Institute
Myriam Hemberger: University of Calgary
Jennifer Hughes: The Babraham Institute
Wendy Dean: The Babraham Institute
Anne Ferguson-Smith: University of Cambridge
Reinald Fundele: Max-Planck-Institut für Molekulare Genetik
Francesca Stewart: The Babraham Institute
Gavin Kelsey: The Babraham Institute
Abigail Fowden: University of Cambridge
Colin Sibley: The University of Manchester, St Mary's Hospital
Wolf Reik: The Babraham Institute

Nature, 2002, vol. 417, issue 6892, 945-948

Abstract: Abstract Imprinted genes in mammals are expressed from only one of the parental chromosomes, and are crucial for placental development and fetal growth1,2,3,4. The insulin-like growth factor II gene (Igf2) is paternally expressed in the fetus and placenta5. Here we show that deletion from the Igf2 gene of a transcript (P0)6,7 specifically expressed in the labyrinthine trophoblast of the placenta leads to reduced growth of the placenta, followed several days later by fetal growth restriction. The fetal to placental weight ratio is thus increased in the absence of the P0 transcript. We show that passive permeability for nutrients of the mutant placenta is decreased, but that secondary active placental amino acid transport is initially upregulated, compensating for the decrease in passive permeability. Later the compensation fails and fetal growth restriction ensues. Our study provides experimental evidence for imprinted gene action in the placenta that directly controls the supply of maternal nutrients to the fetus, and supports the genetic conflict theory of imprinting8. We propose that the Igf2 gene, and perhaps other imprinted genes, control both the placental supply of, and the genetic demand for, maternal nutrients to the mammalian fetus.

Date: 2002
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DOI: 10.1038/nature00819

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