Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes

Ramanathan K. Kasimanickam, Vanmathy R. Kasimanickam, Jacobo S. Rodriguez, Kevin D. Pelzer, Philip D. Sponenberg, Craig Thatcher

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Tocopherols have biphasic, proangiogenic and antiangiogenic therapeutic effects. The objective of this clinical trial was to clarify tocopherol's placental angiogenic potential in late pregnant ewes following oral supplementation.Methods: Eighteen pregnant ewes during late gestation were selected for this study. Ewes were given oral supplementation of 500 mg of alpha-tocopherol (aT; N = 6) or 1000 mg of gamma-tocopherol (gT; N = 7) or placebo (CON; N = 5) once daily from 107 to 137 days post breeding. Serum was obtained at weekly intervals and tissue samples were obtained at the end of supplementation to: 1) evaluate tocopherol concentrations in serum, uterus and placentome; 2) evaluate relative mRNA expressions of Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PlGF), endothelial Nitric Oxide Synthase (eNOS) and Hypoxia Inducible Factors (HIF) in uterus, caruncle and cotyledon; 3) analyze the morphometry of the placental vascular network.Results: Supplementation of aT or gT resulted in increased concentrations in serum, placentome and uterus compared to control (P < 0.05). In aT group, mRNA expressions of PlGF, eNOS and HIF-1α in cotyledon were greater than the CON group. In gT group, mRNA expressions of VEGF, eNOS, HIF-1 alpha and HIF-2 alpha in caruncle and uterus, and HIF-1α in cotyledon, were greater than the CON group. Morphometry analysis revealed increased angiogenesis in the supplemented groups.Conclusion: Daily oral supplementation of aT or gT increased angiogenesis in the placental vascular network in pregnant ewes during late gestation. Increase in placental angiogenesis may provide nutrients required for the development and growth of fetus during late pregnancy.

Original languageEnglish (US)
Article number86
JournalReproductive Biology and Endocrinology
Volume8
DOIs
StatePublished - Jul 12 2010

Fingerprint

Tocopherols
Hypoxia-Inducible Factor 1
Uterus
Blood Vessels
Cotyledon
Nitric Oxide Synthase Type III
Pregnancy
Messenger RNA
Placenta
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Serum
gamma-Tocopherol
alpha-Tocopherol
Therapeutic Uses
Growth and Development
Breeding
Fetus
Placebos
Clinical Trials

ASJC Scopus subject areas

  • Developmental Biology
  • Endocrinology
  • Reproductive Medicine
  • Medicine(all)

Cite this

Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes. / Kasimanickam, Ramanathan K.; Kasimanickam, Vanmathy R.; Rodriguez, Jacobo S.; Pelzer, Kevin D.; Sponenberg, Philip D.; Thatcher, Craig.

In: Reproductive Biology and Endocrinology, Vol. 8, 86, 12.07.2010.

Research output: Contribution to journalArticle

Kasimanickam, Ramanathan K. ; Kasimanickam, Vanmathy R. ; Rodriguez, Jacobo S. ; Pelzer, Kevin D. ; Sponenberg, Philip D. ; Thatcher, Craig. / Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes. In: Reproductive Biology and Endocrinology. 2010 ; Vol. 8.
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abstract = "Background: Tocopherols have biphasic, proangiogenic and antiangiogenic therapeutic effects. The objective of this clinical trial was to clarify tocopherol's placental angiogenic potential in late pregnant ewes following oral supplementation.Methods: Eighteen pregnant ewes during late gestation were selected for this study. Ewes were given oral supplementation of 500 mg of alpha-tocopherol (aT; N = 6) or 1000 mg of gamma-tocopherol (gT; N = 7) or placebo (CON; N = 5) once daily from 107 to 137 days post breeding. Serum was obtained at weekly intervals and tissue samples were obtained at the end of supplementation to: 1) evaluate tocopherol concentrations in serum, uterus and placentome; 2) evaluate relative mRNA expressions of Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PlGF), endothelial Nitric Oxide Synthase (eNOS) and Hypoxia Inducible Factors (HIF) in uterus, caruncle and cotyledon; 3) analyze the morphometry of the placental vascular network.Results: Supplementation of aT or gT resulted in increased concentrations in serum, placentome and uterus compared to control (P < 0.05). In aT group, mRNA expressions of PlGF, eNOS and HIF-1α in cotyledon were greater than the CON group. In gT group, mRNA expressions of VEGF, eNOS, HIF-1 alpha and HIF-2 alpha in caruncle and uterus, and HIF-1α in cotyledon, were greater than the CON group. Morphometry analysis revealed increased angiogenesis in the supplemented groups.Conclusion: Daily oral supplementation of aT or gT increased angiogenesis in the placental vascular network in pregnant ewes during late gestation. Increase in placental angiogenesis may provide nutrients required for the development and growth of fetus during late pregnancy.",
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AU - Sponenberg, Philip D.

AU - Thatcher, Craig

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