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Maternally-inherited Grb10 reduces placental size and efficiency
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The control of foetal growth is poorly understood and yet it is critically important that at birth the body has attained appropriate size and proportions. Growth and survival of the mammalian foetus is dependent upon a functional placenta throughout most of gestation. A few genes are known that influence both foetal and placental growth and might therefore coordinate growth of the conceptus, including the imprinted Igf2 and Grb10 genes. Grb10 encodes a signalling adapter protein, is expressed predominantly from the maternally-inherited allele and acts to restrict foetal and placental growth. Here, we show that following disruption of the maternal allele in mice, the labyrinthine volume was increased in a manner consistent with a cell-autonomous function of Grb10 and the enlarged placenta was more efficient in supporting foetal growth. Thus, Grb10 is the first example of a gene that acts to limit placental size and efficiency. In addition, we found that females inheriting a mutant Grb10 allele from their mother had larger litters and smaller offspring than those inheriting a mutant allele from their father. This grandparental effect suggests Grb10 can influence reproductive strategy through the allocation of maternal resources such that offspring number is offset against size.
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“There is also evidence for inter-sibling competition for nutrients between mutant and wild type fetuses within mixed litters, which affects the size of the wild type pups (14, 104, 124).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [104]
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Evans, B. L., Garner, T., Leonibus, C. D., Wright, L., Sharps, M. C., Wearing, O. H., Ripley, D. M., Shiels, H. A., Hurlstone, A. F. L., Clayton, P., et al. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05784-9
Moorwood, K., Smith, F. M., Garfield, A. S., Cowley, M., Holt, L. J., Daly, R. J., & Ward, A. (2024) · Figshare · doi:10.6084/m9.figshare.27132735
Self-citationBonnet, A., Bluy, L. E., Gress, L., Canario, L., Ravon, L., Sécula, A., Billon, Y., & Liaubet, L. (2024) · Figshare · doi:10.6084/m9.figshare.26696469
Moorwood, K., Smith, F. M., Garfield, A. S., & Ward, A. (2024) · Figshare · doi:10.6084/m9.figshare.26727838
Self-citationAoki, S., Higashimoto, K., Hidaka, H., Ohtsuka, Y., Aoki, S., Mishima, H., Yoshiura, K., Nakabayashi, K., Hata, K., Yatsuki, H., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19785823
Bonnet, A., Bluy, L. E., Gress, L., Canario, L., Ravon, L., Sécula, A., Billon, Y., & Liaubet, L. (2024) · Figshare · doi:10.6084/m9.figshare.25459583
Moorwood, K., Smith, F. M., Garfield, A. S., Cowley, M., Holt, L. J., Daly, R. J., & Ward, A. (2024) · Figshare · doi:10.6084/m9.figshare.27132732
Self-citation
Metadata
- Authors
- Charalambous, M., Cowley, M., Geoghegan, F., Smith, F. M., Radford, E. J., Marlow, B. P., Graham, C. F., Hurst, L. D., & Ward, A.
- Affiliations
- University of Bath (GB)
- University of Cambridge (GB)
- University of Oxford (GB)
- Corresponding author
- Ward, Andrew
- ORCID
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 337
- Issue
- 1
- Pages
- 1-8
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W1983878712
- Cited by
- 101
- References
- 48
- Citations by year
- 2025: 4 · 2024: 12 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 11 · 2013: 6 · 2012: 13
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Funders
- University of Bath
- Directorate for Biological Sciences
- 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
- Grb10, placental development, placental efficiency, maternal allele, insulin-like growth factor II, genomic imprinting, fetal growth, litter size, offspring size, maternal resource allocation, reproductive strategies
- MeSH terms
- Alleles, Animals, Endothelium, Female, Immunohistochemistry, Mice, Inbred CBA, Mice, Inbred C57BL, Placenta, Pregnancy, Genomic Imprinting, Mice, GRB10 Adaptor Protein
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