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

Constância, M., Hemberger, M., Hughes, J., Dean, W., Ferguson-Smith, A., Fundele, R., et al. (2002). Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature, 417(6892), 945-948.

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Constância, Miguel, Author
Hemberger, Myriam, Author
Hughes, Jennifer, Author
Dean, Wendy, Author
Ferguson-Smith, Anne, Author
Fundele, Reinald1, Author              
Stewart, Francesca, Author
Kelsey, Gavin, Author
Fowden, Abigail, Author
Sibley, Colin, Author
Reik, Wolf, Author
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1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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 Abstract: Imprinted genes in mammals are expressed from only one of the parental chromosomes, and are crucial for placental development and fetal growth. The insulin-like growth factor II gene (Igf2) is paternally expressed in the fetus and placenta. Here we show that deletion from the Igf2 gene of a transcript (P0) 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 imprinting. 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.

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Language(s): eng - English
 Dates: 2002-06
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: eDoc: 24158
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 417 (6892) Sequence Number: - Start / End Page: 945 - 948 Identifier: -