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Observational Study
. 2016 Aug 6;8(8):474.
doi: 10.3390/nu8080474.

Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy

Sara Pauwels  1   2 , Radu Corneliu Duca  3 , Roland Devlieger  4   5 , Kathleen Freson  6 , Dany Straetmans  7 , Erik Van Herck  8 , Inge Huybrechts  9 , Gurdun Koppen  10 , Lode Godderis  11   12
Affiliations
Observational Study

Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy

Sara Pauwels et al. Nutrients. .

Abstract

It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13 and weeks 18-22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.

Keywords: global DNA hydroxymethylation; global DNA methylation; methyl-group donor; pregnancy.

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Figures

Figure 1
Figure 1
The one-carbon metabolism and DNA (hydroxy)methylation. BAD, Betaine Aldehyde Dehydrogenase; BHMT, Betaine Homocysteine Methyltransferase; CBS, Cystathionine Beta Synthase; CD, Choline Dehydrogenase; CGL, Cystathionine Gamma Lyase; DHF, dihydrofolate; DHFR, Dihydrofolate Reductase; Dnmt, DNA Methyltransferase; MAT, Methionine Adenosyltransferase; MS, Methionine Synthase; MTHF, Methyltetrahydrofolate; MTHFR, Methylenetetrahydrofolate Reductase; SAH, S-Adenosylhomocysteine; SAM, S-Adenosylmethionine; TET, Ten-eleven Translocation; and THF, Tetrahydrofolate.
Figure 2
Figure 2
Flowchart of women enrolled in the MANOE study and included in the statistical analysis.
Figure 3
Figure 3
Mean DNA methylation percentage and 95%CI before pregnancy (n = 34), during pregnancy, and at delivery (n = 114); * %Global DNA methylation pre-pregnancy higher than %methylation at 12 weeks (p = 0.007), 30 weeks (p = 0.04), and at delivery (p = 0.04); † %Global DNA methylation at 20 weeks (6.69%) higher than %methylation at 12 weeks (p = 0.004), and 30 weeks (p = 0.04).
Figure 4
Figure 4
Mean DNA hydroxymethylation percentage and 95% CI before pregnancy (n = 34), during pregnancy, and at delivery (n = 114); * %Global DNA hydroxymethylation pre-pregnancy was higher than % hydroxymethylation at 12 weeks (p = 0.003), 30 weeks (p = 0.006), and at delivery (p = 0.002); † %Global DNA hydroxymethylation at 20 weeks was higher than %hydroxymethylation at 12 weeks (p = 0.046), and delivery (p = 0.02).
Figure 5
Figure 5
Mean DNA (hydroxy)methylation percentage and 95% CI before pregnancy (n = 34), during each trimester of pregnancy and at delivery (n = 114).
Figure 6
Figure 6
Maternal serum progesterone, estradiol, and β-hCG during pregnancy (n = 30).
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