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Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats
Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in...
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Published in: | PloS one 2011-03, Vol.6 (3), p.e17706-e17706 |
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description | Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p |
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We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0017706</identifier><identifier>PMID: 21423696</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology ; Biomarkers ; Brain ; Brain research ; Cyanocobalamin ; Defects ; Deoxyribonucleic acid ; Diet ; Dietary supplements ; DNA ; DNA Methylation ; Docosahexaenoic acid ; Docosahexaenoic Acids - blood ; Drug dosages ; Epigenetics ; Fatty acids ; Fatty Acids - blood ; Feeding Behavior ; Female ; Folic acid ; Folic Acid - blood ; Gene expression ; Genomes ; Homocysteine ; Homocysteine - blood ; Hypertension ; Insulin resistance ; Laboratory animals ; Ligands ; Medicine ; Metabolism ; Nutrient deficiency ; Nutrition research ; Offspring ; Omega-3 fatty acids ; Placenta ; Placenta - metabolism ; Preeclampsia ; Pregnancy ; Rats ; Reproduction ; Rodents ; Studies ; Vegetarianism ; Vitamin B ; Vitamin B 12 - blood ; Vitamin B12</subject><ispartof>PloS one, 2011-03, Vol.6 (3), p.e17706-e17706</ispartof><rights>2011 Kulkarni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.</description><subject>Animals</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cyanocobalamin</subject><subject>Defects</subject><subject>Deoxyribonucleic acid</subject><subject>Diet</subject><subject>Dietary supplements</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Docosahexaenoic acid</subject><subject>Docosahexaenoic Acids - blood</subject><subject>Drug dosages</subject><subject>Epigenetics</subject><subject>Fatty acids</subject><subject>Fatty Acids - blood</subject><subject>Feeding Behavior</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - blood</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Homocysteine</subject><subject>Homocysteine - blood</subject><subject>Hypertension</subject><subject>Insulin resistance</subject><subject>Laboratory animals</subject><subject>Ligands</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Nutrient deficiency</subject><subject>Nutrition research</subject><subject>Offspring</subject><subject>Omega-3 fatty acids</subject><subject>Placenta</subject><subject>Placenta - 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We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21423696</pmid><doi>10.1371/journal.pone.0017706</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biology Biomarkers Brain Brain research Cyanocobalamin Defects Deoxyribonucleic acid Diet Dietary supplements DNA DNA Methylation Docosahexaenoic acid Docosahexaenoic Acids - blood Drug dosages Epigenetics Fatty acids Fatty Acids - blood Feeding Behavior Female Folic acid Folic Acid - blood Gene expression Genomes Homocysteine Homocysteine - blood Hypertension Insulin resistance Laboratory animals Ligands Medicine Metabolism Nutrient deficiency Nutrition research Offspring Omega-3 fatty acids Placenta Placenta - metabolism Preeclampsia Pregnancy Rats Reproduction Rodents Studies Vegetarianism Vitamin B Vitamin B 12 - blood Vitamin B12 |
title | Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats |
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