Excess Maternal Glucocorticoids in Response to In Utero Undernutrition Inhibit Offspring Angiogenesis
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To test the hypothesis that inhibition of offspring angiogenesis by maternal undernutrition (MUN) is mediated by maternal glucocorticoids, 3 groups of dams were studied: controls received ad libitum food; MUN dams were food restricted by 50% from day 10 of gestation; and metyrapone (MET) dams were food restricted and treated with 0.5 mg/mL of MET, a glucocorticoid synthesis inhibitor. The MUN reduced birth weights, reduced vascular endothelial growth factor (VEGF) abundance in P1 aortas, reduced VEGF and VEGF-R2 abundances in P1 mesenteric arterioles, reduced arteriolar endothelial nitric oxide synthase abundance, reduced microvessel density in the anterior tibialis, reduced endothelial cell branching in culture, reduced arteriolar immunoreactivity for proliferating cell nuclear antigen (PCNA), increased active caspase 3 in P1 mesenteric arterioles, and decreased matrix metalloproteinase (MMP)-2 and MMP-9 abundances in lysates of P1 aortas. All of these effects were prevented by treatment with metyrapone. Collectively, these findings suggest that reduced angiogenesis in MUN offspring involves direct inhibitory effects of maternal glucorticoid on fetal VEGF and its receptors.
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Resultant exposure to elevated levels of cortisol may contribute to developmental programming of the fetal hypothalamic-pituitary-adrenal axis and other organ systems.
“Resultant exposure to elevated levels of cortisol may contribute to developmental programming of the fetal hypothalamic-pituitary-adrenal axis and other organ systems (127, 129, 306).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [306]
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- Seckl JR. 11beta-hydroxysteroid dehydrogenases: changing glu- cocorticoid action. Curr Opin Pharmacol. 2004;4(6):597-602.
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Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717 · see citing works
- Authors
- Khorram, O., Ghazi, R., Chuang, T.-D., Han, G., Naghi, J., Ni, Y., & Pearce, W. J.
- Affiliations
- Harbor–UCLA Medical Center (US)
- Loma Linda University (US)
- Corresponding author
- Khorram, Omid
- Venue
- Reproductive Sciences
- Published
- 2014-05
- Volume
- 21
- Issue
- 5
- Pages
- 601-611
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- PMC
- PMC3984487
- OpenAlex
- W2064190876
- Cited by
- 22
- References
- 71
- Citations by year
- 2026: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 5 · 2014: 1
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproductive Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (4290098)
- National Institutes of Health (HD31226)
- National Institute of Neurological Disorders and Stroke (R01NS076945)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01-HD-31226, R03HD054920, P01HD031226)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- maternal undernutrition, maternal glucocorticoids, angiogenesis, fetal growth restriction, metyrapone, vascular endothelial growth factor, VEGF receptor 2, endothelial nitric oxide synthase, microvessel density, apoptosis, caspase-3, matrix metalloproteinases, aorta, mesenteric arterioles, tibialis anterior
- MeSH terms
- Animals, Cells, Cultured, Female, Fetal Growth Retardation, Glucocorticoids, Maternal-Fetal Exchange, Pregnancy, Biomarkers, Rats, Sprague-Dawley, Neovascularization, Physiologic, Malnutrition, Rats
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