Cited by 1,054Genetic Syndromes and ImprintingPregnancy and preeclampsia studiesBirth, Development, and Health

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

Constância, Miguel, Hemberger, Myriam, Hughes, Jennifer, Dean, Wendy, Ferguson-Smith, Anne, Fundele, Reinald, Stewart, Francesca, Kelsey, Gavin, Fowden, Abigail, Sibley, Colin, Reik, Wolf·2002·Nature

DOI 10.1038/nature00819

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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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Authors: Constância, M., Hemberger, M., Hughes, J., Dean, W., Ferguson-Smith, A., Fundele, R., Stewart, F., Kelsey, G., Fowden, A., Sibley, C., & Reik, W.
Affiliations: Babraham Institute (GB)
University of Calgary (CA)
Max Planck Society (DE)
University of Cambridge (GB)
University of Manchester (GB)
Corresponding author: Constância, Miguel
Reik, Wolf
ORCID: Constância, Miguel
Hemberger, Myriam
Dean, Wendy
Kelsey, Gavin
Fowden, Abigail
Sibley, Colin
Reik, Wolf
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-06
Volume: 417
Issue: 6892
Pages: 945-948
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature00819
OpenAlex: W2092668546
Cited by: 1,054
References: 31
Citations by year: 2026: 15 · 2025: 20 · 2024: 32 · 2023: 42 · 2022: 37 · 2021: 37 · 2020: 36 · 2019: 46 · 2018: 38 · 2017: 42 · 2016: 45 · 2015: 46 · 2014: 41 · 2013: 50 · 2012: 70
FWCI: 24.12
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: Medical Research Council
Biotechnology and Biological Sciences Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: insulin-like growth factor II, genomic imprinting, placental development, fetal growth restriction, amino acid transport
MeSH terms: Alleles, Animals, Biological Transport, Female, Embryonic and Fetal Development, Fetus, Gestational Age, Insulin-Like Growth Factor II, Kinetics, Male, Maternal-Fetal Exchange, Organ Specificity, Permeability, Placenta, Placentation, Pregnancy, RNA, Messenger, Trophoblasts, Gene Deletion, In Situ Hybridization, Mice, Knockout, Genomic Imprinting, Mice

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

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