Raised Late Pregnancy Glucose Concentrations in Mice Carrying Pups With Targeted Disruption of H19 Δ 13
Open accessAbstract
OBJECTIVE: We have hypothesized that variation in imprinted growth-promoting fetal genes may affect maternal glucose concentrations in pregnancy. To test this hypothesis we evaluated the effects of fetal disruption of murine H19Δ13 on maternal glucose concentrations in pregnancy. RESEARCH DESIGN AND METHODS: Experimental mice were pregnant females that had inherited the disrupted H19Δ13 from their fathers and were therefore phenotypically wild type due to imprinting; approximately half of their litters were null for H19Δ13 through maternal inheritance of the disrupted gene. In control mice approximately half the litter paternally inherited the disrupted H19Δ13, so the pups were either genetically wild type or phenotypically wild type due to imprinting. Blood glucose concentrations were assessed by intraperitoneal glucose tolerance tests on days 1, 16, and 18 of pregnancy. RESULTS: There were no differences in the glucose concentrations of control and experimental pregnant mice at day 1. However, at day 16 mothers carrying H19Δ13-null pups had a significantly higher area under the glucose tolerance test curves than controls (1,845 ± 378 vs. 1,386 ± 107 mmol · min · l−1 [P = 0.01]) in association with increasing pregnancy-related insulin resistance. Although this difference lessened toward term, overall, mothers of maternally inherited H19Δ13 mutants had significantly higher glucose concentrations during the last trimester (1,602 ± 321 [n = 17] vs. 1,359 ± 147 [n = 18] mmol · min · l−1 [P = 0.009]). CONCLUSIONS: This study provides evidence that maternal glucose concentrations in pregnant mice can be affected by targeted disruption of fetal H19Δ13. This implies that variable fetal IGF2 expression could affect risk for gestational diabetes.
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Variations in fetal-placental growth induced genetically are known to alter the metabolic and endocrine environment of the dam.
“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 [439]
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Fetal manipulation of maternal metabolism is a critical function of Igf2 imprintingPreprint
López‐Tello, J., Yong, H. E. J., Sandovici, I., Christoforou, E. R., Salazar‐Petres, E., Boyland, R., Napso, T., Constância, M., & Sferruzzi-Perri, A. N. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.19.537510
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- Authors
- Petry, C. J., Evans, M. L., Wingate, D. L., Ong, K. K., Reik, W., Constância, M., & Dunger, D. B.
- Affiliations
- University of Cambridge (GB)
- Babraham Institute (GB)
- Corresponding author
- Petry, Clive J.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-09-30
- Volume
- 59
- Issue
- 1
- Pages
- 282-286
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2797934
- OpenAlex
- W2103583984
- Cited by
- 44
- References
- 30
- Citations by year
- 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 9 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0508-10274)
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/H003312/1)
- 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 › Gestational Diabetes Research and Management
- Keywords
- H19, genomic imprinting, maternal blood glucose, late pregnancy, gestational diabetes mellitus, insulin-like growth factor II, insulin resistance, maternal inheritance, glucose tolerance
- MeSH terms
- Animals, Blood Glucose, Female, Fetus, Glucose Tolerance Test, Hyperglycemia, Insulin, Insulin-Like Growth Factor II, Male, Pedigree, Pregnancy, Pregnancy Complications, Genetic Variation, Diabetes, Gestational, Genome, Genomic Imprinting, RNA, Untranslated, Mice, RNA, Long Noncoding
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