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Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes.

Kasimanickam RK, Kasimanickam VR, Rodriguez JS, Pelzer KD, Sponenberg PD, Thatcher CD - Reprod. Biol. Endocrinol. (2010)

Bottom Line: Tocopherols have biphasic, proangiogenic and antiangiogenic therapeutic effects.In aT group, mRNA expressions of PlGF, eNOS and HIF-1alpha in cotyledon were greater than the CON group.Increase in placental angiogenesis may provide nutrients required for the development and growth of fetus during late pregnancy.

View Article: PubMed Central - HTML - PubMed

Affiliation: College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. ramkasi@vetmed.wsu.edu

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-1alpha 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-1alpha 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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Serum tocopherol concentrations in late pregnant ewes supplemented with alpha tocopherol, gamma tocopherol or placebo. a. Serum alpha tocopherol concentrations (mg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- aT group significantly different from gT and CON group (P < 0.001); ab - Median values with different superscripts were significantly different between days post breeding within aT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo; b. Serum gamma tocopherol concentration (μg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- gT group significantly different from aT and CON group (P < 0.001); Median values with different letters were significantly different between days post breeding within gT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo.
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Figure 4: Serum tocopherol concentrations in late pregnant ewes supplemented with alpha tocopherol, gamma tocopherol or placebo. a. Serum alpha tocopherol concentrations (mg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- aT group significantly different from gT and CON group (P < 0.001); ab - Median values with different superscripts were significantly different between days post breeding within aT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo; b. Serum gamma tocopherol concentration (μg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- gT group significantly different from aT and CON group (P < 0.001); Median values with different letters were significantly different between days post breeding within gT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo.

Mentions: Pair-wise comparisons of the median (25th, 75th percentile) serum aT concentrations (excluding pre-supplementation level) were significantly higher for ewes in aT group compared to ewes in gT and CON groups during the trial period for the respective stages (P < 0.001; Figure 4a and additional file 4, Table S4). Pair-wise comparison of median tocopherol levels between stages within treatment groups was different for the aT group (P < 0.05) but not in gT and CON groups (P > 0.05). Similarly, pair-wise comparisons of the median (25th, 75th percentile) serum gT concentrations (excluding pre-supplementation level) were significantly higher for ewes in the gT group compared to ewes in aT and CON groups during the trial period for the respective stages (Figure 4b and additional file 4, Table S4). Pair-wise comparison of median tocopherol levels between stages within treatment groups was different for the gT group (P < 0.05) but not in aT and CON groups (P > 0.1).


Tocopherol induced angiogenesis in placental vascular network in late pregnant ewes.

Kasimanickam RK, Kasimanickam VR, Rodriguez JS, Pelzer KD, Sponenberg PD, Thatcher CD - Reprod. Biol. Endocrinol. (2010)

Serum tocopherol concentrations in late pregnant ewes supplemented with alpha tocopherol, gamma tocopherol or placebo. a. Serum alpha tocopherol concentrations (mg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- aT group significantly different from gT and CON group (P < 0.001); ab - Median values with different superscripts were significantly different between days post breeding within aT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo; b. Serum gamma tocopherol concentration (μg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- gT group significantly different from aT and CON group (P < 0.001); Median values with different letters were significantly different between days post breeding within gT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2913989&req=5

Figure 4: Serum tocopherol concentrations in late pregnant ewes supplemented with alpha tocopherol, gamma tocopherol or placebo. a. Serum alpha tocopherol concentrations (mg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- aT group significantly different from gT and CON group (P < 0.001); ab - Median values with different superscripts were significantly different between days post breeding within aT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo; b. Serum gamma tocopherol concentration (μg/kg) during late pregnancy in supplemented ewes. Line graphs represent median (25th,75th percentile); *- gT group significantly different from aT and CON group (P < 0.001); Median values with different letters were significantly different between days post breeding within gT group (P < 0.05); No differences between days post breeding were observed for gT and CON groups; Bar - 25th and 75th percentile; dpb - days post breeding; aT - alpha tocoperhol; gT - gamma tocopherol; CON - placebo.
Mentions: Pair-wise comparisons of the median (25th, 75th percentile) serum aT concentrations (excluding pre-supplementation level) were significantly higher for ewes in aT group compared to ewes in gT and CON groups during the trial period for the respective stages (P < 0.001; Figure 4a and additional file 4, Table S4). Pair-wise comparison of median tocopherol levels between stages within treatment groups was different for the aT group (P < 0.05) but not in gT and CON groups (P > 0.05). Similarly, pair-wise comparisons of the median (25th, 75th percentile) serum gT concentrations (excluding pre-supplementation level) were significantly higher for ewes in the gT group compared to ewes in aT and CON groups during the trial period for the respective stages (Figure 4b and additional file 4, Table S4). Pair-wise comparison of median tocopherol levels between stages within treatment groups was different for the gT group (P < 0.05) but not in aT and CON groups (P > 0.1).

Bottom Line: Tocopherols have biphasic, proangiogenic and antiangiogenic therapeutic effects.In aT group, mRNA expressions of PlGF, eNOS and HIF-1alpha in cotyledon were greater than the CON group.Increase in placental angiogenesis may provide nutrients required for the development and growth of fetus during late pregnancy.

View Article: PubMed Central - HTML - PubMed

Affiliation: College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. ramkasi@vetmed.wsu.edu

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-1alpha 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-1alpha 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.

Show MeSH
Related in: MedlinePlus