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Excess Maternal Glucocorticoids in Response to In Utero Undernutrition Inhibit Offspring Angiogenesis

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, La Biomedical Institute, Harbor-UCLA Medical Center, CA, 1000W. Carson St, Box 489, 90502, Torrance, USA

    Omid Khorram MD, PhD, Reza Ghazi MD, Tsai-Der Chuang PhD, Guang Han MD, Joshua Naghi MD & Youping Ni MD, PhD

  2. Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA

    William J. Pearce PhD

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  1. Omid Khorram MD, PhD
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  2. Reza Ghazi MD
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Correspondence to Omid Khorram MD, PhD.

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Khorram, O., Ghazi, R., Chuang, TD. et al. Excess Maternal Glucocorticoids in Response to In Utero Undernutrition Inhibit Offspring Angiogenesis. Reprod. Sci. 21, 601–611 (2014). https://doi.org/10.1177/1933719113508819

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