Expression of DNA methyltransferases in the mouse uterus during early pregnancy and susceptibility to dietary folate deficiency

Abstract

<jats:p>We have characterized the uterine expression of DNA methyltransferases (DNMTs) during early pregnancy in mice and determined whether a folate-deficient diet (FDD) can affect DNMTs in this context. Within endometrial cells, expressions of DNMT (cytosine-5) 1 (<jats:italic>Dnmt</jats:italic><jats:italic>1</jats:italic>),<jats:italic>Dnmt3a</jats:italic>, and<jats:italic>Dnmt</jats:italic><jats:italic>3b</jats:italic>were significantly elevated during the prereceptive phase of pregnancy but generally returned to baseline levels during receptive and postimplantation periods. As such, the transcription of DNMT genes is temporally regulated during early pregnancy. When comparisons were made between implantation sites (IS) and inter-IS on day 5 of pregnancy, lower levels of<jats:italic>Dnmt3a</jats:italic>were detected at IS. Comparisons between IS and inter-IS did not reveal significant expression differences for other DNMT genes. When tissue sections were examined, DNMT3A was specifically lower in the stroma of IS. Reduced DNMT1 and DNMT3B levels were also observed in the luminal and glandular epithelia of IS, whereas no obvious differences in the stroma were detected. In pseudo-pregnant mice subjected to a FDD, levels of<jats:italic>Dnmt</jats:italic><jats:italic>1</jats:italic>and<jats:italic>Dnmt</jats:italic><jats:italic>3a</jats:italic>(but not<jats:italic>Dnmt</jats:italic><jats:italic>3b</jats:italic>) were significantly upregulated in endometrial tissues, as compared with controls. When tissues from these folate-deficient mice were examined, DNMT1 levels were elevated in both the luminal and glandular epithelia, whereas DNMT3A was upregulated in the luminal epithelium and the stroma. A slight increase in DNMT3B levels was detected in the glandular epithelium. These results indicate that DNMTs may regulate the transcription of endometrial genes associated with embryo implantation and that levels of DNMTs are affected by dietary folate in mice.</jats:p>

Gene promoter methylation and DNA repair capacity in monozygotic twins with discordant smoking habits

“…It has been hypothesized that folate deficiency may lead to a deregulation of the intracellular concentration of free SAM and S-adenosylhomocysteine (SAH, an inhibitor of SAM) [51], or to the compensatory up-regulation of DNA methyltransferase (DNMT) [52]: in both cases these events would result in DNA hypermethylation. This hypothesis is in agreement with the observed up-regulation of DNMT1 and DNMT3A in mice subjected to a folate deficient diet [53]. On the other hand, an indirect effect of folate status on DNA methylation via its influence on DRC capacity can be ruled out, as plasma folic acid proved not to affect DRC in this study population [30].…”

Claudin 5 Transcripts Following Acrolein Exposure Affected by Epigenetic Enzyme

“…Aging [23], smoking [24,25], and heavy metal exposure [26,27], acrolein [28,29] have all been associated with changes in the DNA methylome, and with changes in DNMT expression, but the mechanisms by which these changes occur are largely unknown. DNA methyltransferases (DNMTs) such as DNMT1, DNMT3A and DNMT3B contribute to various physiologic and pathologic conditions including embryo implantation [30], cytomegalovirus infection [31], radiation [32], cancer, aging, neural cell differentiation [33]. In this study although DNMT3b was increased at 1 h, 2 h, and 4 h, and DNMT1 was not changed compared to control in acrolein 30 nm exposure.…”

Gene variants in the folate pathway are associated with increased levels of folate receptor autoantibodies

“…DNA (cytosine‐5)‐methyltransferase‐3A ( DNMT3A) belongs to a family of genes that encode enzymes involved in the de novo methylation of S‐adenosyl methionine during development (Ding et al, ). The TT genotype at DNMT3A rs7560488 has been previously found to be associated with an increased risk of myelomeningocele (Pangilinan et al, ).…”

“…Mutations at MTHFR rs1801133 are related to elevated Hcy concentrations which may promote homocysteinylation of the FR such that the modified FAs may act as neo-antigens capable of inducing the production of FR autoantibodies. DNA (cytosine-5)-methyltransferase-3A (DNMT3A) belongs to a family of genes that encode enzymes involved in the de novo methylation of S-adenosyl methionine during development (Ding et al, 2012). The TT genotype at DNMT3A rs7560488 has been previously found to be associated with an increased risk of myelomeningocele (Pangilinan et al, 2012).…”