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methyl tetrahydrofolate reductase and pregnancy

Edouard J Servy, Laetitia Jacquesson-Fournols, Marc Cohen, Yves J R Menezo
PURPOSE: To evaluate the possibility of correcting metabolic defects in gametes and embryos due to methylene tetra hydrofolate reductase (MTHFR) isoforms C677T and A1298C, by supplementation with 5-methyl THF instead of synthetic folic acid. In these couples, high doses of folic acid lead to UMFA (un-metabolized folic acid) syndrome. METHODS: Thirty couples with fertility problems lasting for at least 4 years, such as recurrent fetal loss, premature ovarian insufficiency, or abnormal sperm parameters, with two thirds of them having failed assisted reproductive technology (ART) attempts were included in this program...
June 7, 2018: Journal of Assisted Reproduction and Genetics
Miriam Pertegal, Francisco J Fenoy, Moisés Hernández, Jaime Mendiola, Juan L Delgado, Bárbara Bonacasa, Andrés Corno, Bernardo López, Vicente Bosch, Isabel Hernández
OBJECTIVE: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels. DESIGN: Prospective case-control study. SETTING: University hospital. PATIENT(S): A total of 53 preeclamptic and 72 normal pregnant women...
January 2016: Fertility and Sterility
G Szabó, L Lazar, B Nagy, J Rigo
INTRODUCTION: One-carbon cycle is involved in two essential physiological processes: The synthesis of purins and pyrimidines required for DNA synthesis and repair. The other is the methylation with the methionine cycle. These one-carbon groups are served by the tetrahydrofolate and the S-adenosylmethionine. Deficiencies of the folate, or other abnormalities within the methionine pathway lead to elevated homocysteine levels. These disorders have been implicated in placental diseases. Earlier studies have shown that homocysteine levels are elevated by patients with severe pre-eclampsia than by healthy pregnant normotensive women...
July 2012: Pregnancy Hypertension
Leslie P Stone, P Michael Stone, Emily A Rydbom, Lucas A Stone, T Elliot Stone, Lindsey E Wilkens, Kathryn Reynolds
A retrospective chart review analyzed the effect of customized nutrition on the incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small- and large-for-gestational-age (SGA, LGA) neonates, examining consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low-risk community hospital. The population was divided into 3 groups: (1) study group (SG), (2) private practice (PP), and (3) community healthcare clinic (CHCC). All groups received standard perinatal management, but additionally the study group was analyzed for serum zinc, carnitine, total 25-hydroxy cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O-methyl transferase polymorphisms in the first trimester prior to intervention, with subsequent second trimester and postpartum assessment of zinc, carnitine, and 25 OH-D after intervention...
November 2014: Global Advances in Health and Medicine: Improving Healthcare Outcomes Worldwide
Vinita Khot, Anvita Kale, Asmita Joshi, Preeti Chavan-Gautam, Sadhana Joshi
We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels...
2014: BioMed Research International
Brenda A Hartman, Zia Fazili, Christine M Pfeiffer, Deborah L O'Connor
It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid...
September 2014: Journal of Nutrition
Seema Bhargava, S C Tyagi
Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase...
February 2014: Molecular and Cellular Biochemistry
K E Christensen, L Deng, K Y Leung, E Arning, T Bottiglieri, O V Malysheva, M A Caudill, N I Krupenko, N D Greene, L Jerome-Majewska, R E MacKenzie, R Rozen
Genetic variants in one-carbon folate metabolism have been identified as risk factors for disease because they may impair the production or use of one-carbon folates required for nucleotide synthesis and methylation. p.R653Q (1958G>A) is a single-nucleotide polymorphism (SNP) in the 10-formyltetrahydrofolate (formylTHF) synthetase domain of the trifunctional enzyme MTHFD1; this domain produces the formylTHF which is required for the de novo synthesis of purines. Approximately 20% of Caucasians are homozygous for the Q allele...
September 15, 2013: Human Molecular Genetics
Klaus Pietrzik, Lynn Bailey, Barry Shane
There is a large body of evidence to suggest that improving periconceptional folate status reduces the risk of neonatal neural tube defects. Thus increased folate intake is now recommended before and during the early stages of pregnancy, through folic acid supplements or fortified foods. Furthermore, there is growing evidence that folic acid may have a role in the prevention of other diseases, including dementia and certain types of cancer. Folic acid is a synthetic form of the vitamin, which is only found in fortified foods, supplements and pharmaceuticals...
August 2010: Clinical Pharmacokinetics
N Solanky, A Requena Jimenez, S W D'Souza, C P Sibley, J D Glazier
Poor folate status during pregnancy can lead to elevated maternal plasma levels of homocysteine (Hcy) with associated pregnancy complications and adverse neonatal outcomes, suggesting placental metabolism of Hcy might be an important determinant in influencing fetal development. The metabolic pathways for Hcy in placenta are not well defined. In this study we examined the gene expression of key enzymes involved in Hcy metabolism in first trimester and term human placenta to determine which metabolic pathways prevail...
February 2010: Placenta
Sébastien Blaise, Jean-Marc Alberto, Emmanuelle Nédélec, Ahmet Ayav, Grégory Pourié, Jean-Pierre Bronowicki, Jean-Louis Guéant, Jean-Luc Daval
Elevated plasma homocysteine has been linked to pregnancy complications and developmental diseases. Whereas hyperhomocysteinemia is frequently observed in populations at risk of malnutrition, hypoxia may alter the remethylation of homocysteine in hepatocytes. We aimed to investigate the combined influences of early deficiency in nutritional determinants of hyperhomocysteinemia and of neonatal hypoxia on homocysteine metabolic pathways in developing rats. Dams were fed a standard diet or a diet deficient in vitamins B12, B2, folate, month, and choline from 1 mo before pregnancy until weaning of the offspring...
June 2005: Pediatric Research
E Mierzejewska
Folic acid supplementation before conception and during the first trimester of pregnancy prevents about 70% of all neural tube defects (NTD). Folic acid is a cofactor in the homocysteine metabolism. Its product--S-adenosylmethionine is a major methyl donor for reactions taking place in a cell. The 677 C-->T mutation in the methylene tetrahydrofolate reductase gene leads to thermolability and decreased activity of the enzyme. In the individuals homozygous for that mutation hyperhomocystynemia and lowered plasma folate level are observed...
October 1999: Medycyna Wieku Rozwojowego
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