The role and interaction of imprinted genes in human fetal growth
Open accessAbstract
Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 ( IGF2 ), its receptor IGF2R , and the IGF2 / IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 ( PHLDA2 ), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 ( GRB10 ) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue ( DLK1 ) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects.
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Imprinted genes are known to have a disproportionately important role in fetal-placental development and are involved in resource allocation more widely.
“These studies have tended to concentrate on the imprinted genes, which are known to have a disproportionately important role in fetal-placental development and are involved in resource allocation more widely (126, 189, 385, 544).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [385]
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References 75 · Cited by 155
- Authors
- Moore, G. E., Ishida, M., Demetriou, C., Al-Olabi, L., Leon, L. J., Thomas, A. C., Abu-Amero, S., Frost, J. M., Stafford, J. L., Chaoqun, Y., Duncan, A. J., Baigel, R., Brimioulle, M., Iglesias-Platas, I., Apostolidou, S., Aggarwal, R., Whittaker, J. C., Syngelaki, A., Nicolaides, K. H., Regan, L., Monk, D., & Stanier, P.
- Affiliations
- University College London (GB)
- Genetics and Epigenetics in Health and Diseases Section, Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London WC1N 1EH, UK
- University of London (GB)
- Harris Birthright Research Centre for Fetal Medicine (GB)
- Imperial College London (GB)
- Corresponding author
- Moore, Gudrun E.
- ORCID
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2015-03-05
- Volume
- 370
- Issue
- 1663
- Pages
- 20140074
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC4305174
- OpenAlex
- W2141298577
- Cited by
- 155
- References
- 75
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 17 · 2021: 14 · 2020: 8 · 2019: 21 · 2018: 14 · 2017: 14 · 2016: 14 · 2015: 12
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- March of Dimes Foundation
- Wellcome Trust
- Wellbeing of Women
- Great Ormond Street Hospital Charity
- Great Ormond Street Hospital for Children
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- genomic imprinting, imprinted genes, fetal growth, insulin-like growth factor II, IGF-II receptor, PHLDA2, Grb10, DLK1, birth weight, crown-rump length, head circumference, chorionic villus sampling, placenta, parent-of-origin effects, fetal growth restriction, single nucleotide polymorphisms
- MeSH terms
- Birth Weight, Calcium-Binding Proteins, Chorionic Villi, Female, Humans, Insulin-Like Growth Factor II, Membrane Proteins, Nuclear Proteins, Placenta, Pregnancy, Receptors, Somatomedin, Genomic Imprinting, Gene Expression Regulation, Developmental, Intercellular Signaling Peptides and Proteins, Fetal Development
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