Journal
REPRODUCTIVE SCIENCES
Volume 21, Issue 5, Pages 601-611Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719113508819
Keywords
angiogenesis; fetal programming; glucocorticoids; maternal undernutrition; matrix metalloproteinases; VEGF
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Funding
- NIH [1RO3 HD054920-01]
- American Heart Association Western Affiliate [4290098]
- [PO1-HD31226]
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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 PI aortas, reduced VEGF and VEGF-R2 abundances in PI 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 PI mesenteric arterioles, and decreased matrix metalloproteinase (MMP)-2 and MMP-9 abundances in lysates of PI 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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