The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Placental-Specific Igf2 Deficiency Alters Developmental Adaptations to Undernutrition in Mice
Abstract
The pattern of fetal growth is a major determinant of the subsequent health of the infant. We recently showed in undernourished (UN) mice that fetal growth is maintained until late pregnancy, despite reduced placental weight, through adaptive up-regulation of placental nutrient transfer. Here, we determine the role of the placental-specific transcript of IGF-II (Igf2P0), a major regulator of placental transport capacity in mice, in adapting placental phenotype to UN. We compared the morphological and functional responses of the wild-type (WT) and Igf2P0-deficient placenta in WT mice fed ad libitium or 80% of the ad libitium intake. We observed that deletion of Igf2P0 prevented up-regulation of amino acid transfer normally seen in UN WT placenta. This was associated with a reduction in the proportion of the placenta dedicated to nutrient transport, the labyrinthine zone, and its constituent volume of trophoblast in Igf2P0-deficient placentas exposed to UN on d 16 of pregnancy. Additionally, Igf2P0-deficient placentas failed to up-regulate their expression of the amino acid transporter gene, Slc38a2, and down-regulate phosphoinositide 3-kinase-protein kinase B signaling in response to nutrient restriction on d 19. Furthermore, deleting Igf2P0 altered maternal concentrations of hormones (insulin and corticosterone) and metabolites (glucose) in both nutritional states. Therefore, Igf2P0 plays important roles in adapting placental nutrient transfer capacity during UN, via actions directly on the placenta and/or indirectly through the mother.
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“Evidence from downstream signaling indicates that nutrient restriction leads to reduced mTOR activity, along with reduced insulin and AKT signaling, in rats fed a low protein diet (470), and mice fed 80% of the control ad libitum diet (495), as might be expected.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [495]
In the citing paper
“Certainly, the changes in the placental capacity for nutrient transfer induced by maternal undernutrition do not occur in the Igf2P0 null mutant (495).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [495]
In the citing paper
“In addition, variations in fetal-placental growth induced genetically are known to alter the metabolic and endocrine environment of the dam (439, 495).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [495]
In the citing paper
“Certainly, upregulation of placental amino acid transport is maintained until D19 in mice with complete Igf2P0null litters but not in Igf2P0 mutants of dams with mixed litters of mutants and wild types, which have a greater total conceptus mass and, thus, demand for nutrients in late gestation (124, 495).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [495]
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Metadata
- Authors
- Sferruzzi-Perri, A. N., Vaughan, O. R., Coan, P. M., Suciu, M. C., Darbyshire, R., Constancia, M., Burton, G. J., & Fowden, A. L.
- Affiliations
- University of Cambridge (GB)
- Centre for Trophoblast Research (A.N.S.-P., O.R.V., P.M.C., M.C.S., R.D., M.C., G.J.B., A.L.F.), Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom;
- Corresponding author
- Sferruzzi-Perri, A. N.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2011-06-14
- Volume
- 152
- Issue
- 8
- Pages
- 3202-3212
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1999065094
- Cited by
- 115
- References
- 66
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 13 · 2021: 6 · 2020: 11 · 2019: 4 · 2018: 13 · 2017: 8 · 2016: 10 · 2015: 11 · 2014: 2 · 2013: 8 · 2012: 9
- FWCI
- 6.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/B50118X/1, BB/C513626/1, BB/B50118X/2)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- malnutrition, placental nutrient transfer, amino acid transport, SLC38A2, trophoblast, labyrinth zone, fetal growth, maternal insulin, corticosterone, maternal blood glucose, placental development
- MeSH terms
- Adaptation, Physiological, Amino Acids, Animals, Biological Transport, Female, Insulin-Like Growth Factor II, Male, Mice, Inbred C57BL, Placenta, Pregnancy, Phosphatidylinositol 3-Kinases, Malnutrition, Proto-Oncogene Proteins c-akt, Mice
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