title: Excess maternal glucocorticoids in response to in utero undernutrition inhibit offspring angiogenesis.
abstract: 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.
authors.affiliation: 1Department of Obstetrics and Gynecology, La Biomedical Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Khorram
authors.forename: Reza
authors.initials: R
authors.lastname: Ghazi
authors.forename: Tsai-Der
authors.initials: TD
authors.lastname: Chuang
authors.forename: Guang
authors.initials: G
authors.lastname: Han
authors.forename: Joshua
authors.initials: J
authors.lastname: Naghi
authors.forename: Youping
authors.initials: Y
authors.lastname: Ni
authors.forename: William J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D005938:Glucocorticoids / Q000378:metabolism*; D044342:Malnutrition / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids
keywords: VEGF; angiogenesis; fetal programming; glucocorticoids; maternal undernutrition; matrix metalloproteinases