Placental-specific IGF-II is a major modulator of placental and fetal growth
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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Comparison of the placental-specific Igf2P0 with the complete Igf2 null mutant demonstrates that the small placenta can become more efficient by increasing its nutrient transfer and transporter abundance when there is a maintained drive for growth by feto-placental tissues still expressing Igf2.
“Comparison of the placental-specific Igf2P0 with the complete Igf2 null mutant demonstrates clearly that the small placenta can become more efficient by increasing its nutrient transfer and transporter abundance when there is a maintained drive for growth by feto-placental tissues still expressing Igf2 (124, 125).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [125]
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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
- Venue
- Nature
- Published
- 2002-06
- Volume
- 417
- Issue
- 6892
- Pages
- 945-948
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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