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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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Related in: MedlinePlus

Schematic representation of treatment regimen and sample collection. dpb - days post breeding.
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Figure 1: Schematic representation of treatment regimen and sample collection. dpb - days post breeding.

Mentions: The ewes were randomly assigned to three groups: 1) aT group (n = 6) - received 500 mg of aT (Nature's Bounty, Bohemia, NY 11716), 2) gT group (n = 7) - received 1000 mg of gT (Kemin Industries Inc., Des Moines, Iowa 50317), 3) Control (CON) group (n = 5) - received a placebo. The average tocopherols concentrations in the supplement is given in Additional file 2, Table S2. Animals were supplemented orally, once daily, from approximately 100 to 137 days post breeding (dpb) (Figure 1). Blood samples were collected one week prior to onset of supplementation and then weekly until the end of the supplementation period [94 dpb (presupplement level), 107 dpb, 114 dpb, 121 dpb, 128 dpb, 136 ± 1 dpb] for serum aT and gT evaluation (Figure 1). At the end of the supplementation period (136 ± 1), all ewes were euthanized and tissue samples were collected from the gravid uterus and placentomes to evaluate aT and gT concentrations. Tissue samples were snap frozen and stored at -70°C until analysis. Caruncle, cotyledon and intercaruncular uterus samples were also collected and stored in RNAlater (Qiagen Inc., Valencia, CA 91355) and frozen at -70°C to evaluate mRNA expression. Cotyledones were separated from caruncles by applying strong pressure. Placentomal and uterine tissues were collected close to the umbilical cord for consistency.


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)

Schematic representation of treatment regimen and sample collection. dpb - days post breeding.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913989&req=5

Figure 1: Schematic representation of treatment regimen and sample collection. dpb - days post breeding.
Mentions: The ewes were randomly assigned to three groups: 1) aT group (n = 6) - received 500 mg of aT (Nature's Bounty, Bohemia, NY 11716), 2) gT group (n = 7) - received 1000 mg of gT (Kemin Industries Inc., Des Moines, Iowa 50317), 3) Control (CON) group (n = 5) - received a placebo. The average tocopherols concentrations in the supplement is given in Additional file 2, Table S2. Animals were supplemented orally, once daily, from approximately 100 to 137 days post breeding (dpb) (Figure 1). Blood samples were collected one week prior to onset of supplementation and then weekly until the end of the supplementation period [94 dpb (presupplement level), 107 dpb, 114 dpb, 121 dpb, 128 dpb, 136 ± 1 dpb] for serum aT and gT evaluation (Figure 1). At the end of the supplementation period (136 ± 1), all ewes were euthanized and tissue samples were collected from the gravid uterus and placentomes to evaluate aT and gT concentrations. Tissue samples were snap frozen and stored at -70°C until analysis. Caruncle, cotyledon and intercaruncular uterus samples were also collected and stored in RNAlater (Qiagen Inc., Valencia, CA 91355) and frozen at -70°C to evaluate mRNA expression. Cotyledones were separated from caruncles by applying strong pressure. Placentomal and uterine tissues were collected close to the umbilical cord for consistency.

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