The Effects of Melatonin on the Teratogenic Effects of Homocysteine

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Authors
Carter, Katherine Margaret
Issue Date
2010-03-14
Type
Thesis
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en_US
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Abstract
While folic acid deficiency has long been connected with adverse outcomes of pregnancy, evidence indicates homocysteine is the teratogenic agent in folic acid deficiency and maternal hyperhomocysteinemia has been shown to result in fetal death and congenital defects. To date, the mechanism of homocysteine teratogenicity is unclear. Hyperhomocysteinemia is also associated with several other disease states, including cardiovascular and neurodegenerative diseases. It has been proposed that the mechanism of homocysteine pathogenesis within these disease states results from the auto-oxidation of homocysteine and subsequently increases in oxidative stress. Melatonin is a powerful antioxidant, shown to be effective in decreasing pro-oxidant effects of homocysteine within cardiovascular and neurodegenerative diseases. In this thesis project, avian embryos were treated with homocysteine during neurulation. Homocysteine treatment resulted in dose-dependent mortality and disruption of normal development of embryonic development, conferring specific defects such as neural tube defects, caudal cysts, and decreases in extraembryonic vasculature. Melatonin and ascorbic acid, two antioxidants, were shown to reduce homocysteine induced mortality. Furthermore, experiments attempting to rescue decreased extraembryonic vasculature, although underpowered and unable to detect a significant difference, trended toward increasing vascular density. In summary, embryonic treatment with antioxidants such as melatonin and ascorbic acid during neurulation reduces the effects of homocysteine on the developing embryo. These results are suggestive of a role for oxidative stress in the mechanism of homocysteine teratogenicity.
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Creighton University
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copyright Katherine M. Carter
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