Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

Castaño, Erika; Caviedes, Lorena; Hirsch, Steffen; Llanos, Miguel; Íñiguez, Germán; Ronco, Ana María

doi:10.1371/journal.pone.0170389

Cited by 24 publications

(23 citation statements)

References 49 publications

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“…Deficiencies in one carbon metabolites have been associated with increased risk for a range of poor health outcomes, including vascular disease, megaloblastic anemia, and certain types of cancer in adults 7 . The consequences of deficiencies in one-carbon metabolism are even more pronounced during intrauterine development, as folate deficiencies have been associated with a range of pregnancy complications including preterm birth and neural tube defects 1 , 7 – 11 .…”

Section: Introductionmentioning

confidence: 99%

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Knight

Park

Hausman

et al. 2018

Sci Rep

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One-carbon metabolism is essential for multiple cellular processes and can be assessed by the concentration of folate metabolites in the blood. One-carbon metabolites serve as methyl donors that are required for epigenetic regulation. Deficiencies in these metabolites are associated with a variety of poor health outcomes, including adverse pregnancy complications. DNA methylation is known to vary with one-carbon metabolite concentration, and therefore may modulate the risk of adverse pregnancy outcomes. This study addresses changes in one-carbon indices over pregnancy and the relationship between maternal and child DNA methylation and metabolite concentrations by leveraging data from 24 mother-infant dyads. Five of the 13 metabolites measured from maternal blood and methylation levels of 993 CpG sites changed over the course of pregnancy. In dyads, maternal and fetal one-carbon concentrations were highly correlated, both early in pregnancy and at delivery. The 993 CpG sites whose methylation levels changed over pregnancy in maternal blood were also investigated for associations with metabolite concentrations in infant blood at delivery, where five CpG sites were associated with the concentration of at least one metabolite. Identification of CpG sites that change over pregnancy may result in better characterization of genes and pathways involved in maintaining a healthy, term pregnancy.

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Section: Introductionmentioning

confidence: 99%

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Knight

Park

Hausman

et al. 2018

Sci Rep

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“…Folates are transferred from the mother to the fetus through the placenta via 3 specific transporters (RFC, FOLR1, PCFT/HCP1) 18 in addition to additional efflux transporters belonging to the ABC superfamily that are present in the human placenta 19 . In our laboratory, we have found that placental folate transport varies according to birth weight 20 and gestational age 21 . In addition, preterm newborns (32-36 weeks of gestation) had higher serum folate levels and lower vitamin B12 levels compared to serum concentrations in term newborns 21 .…”

Section: Transport Of Folate To the Fetusmentioning

confidence: 97%

“…In our laboratory, we have found that placental folate transport varies according to birth weight 20 and gestational age 21 . In addition, preterm newborns (32-36 weeks of gestation) had higher serum folate levels and lower vitamin B12 levels compared to serum concentrations in term newborns 21 . The same was observed in small term infants for gestational age (SGA) compared to adequate term gestational age (AGA) infants 20 .…”

Section: Transport Of Folate To the Fetusmentioning

confidence: 97%

Folatos y Embarazo, conceptos actuales: ¿Es necesaria una suplementación con Acido Fólico?

Castaño

Piñuñuri

Hirsch

et al. 2017

Rev. chil. pediatr.

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Folate intake during pregnancy is essential for an adequate fetal and placental development and for the long time health of the individual. Its deficiency may induce fetal pathologies, including neural tube disease (NTD). Therefore, several countries implemented public policies to fortify foods with folic acid (FA). Chile started the fortification of wheat flour with FA in the year 2000, decreasing a 43% the prevalence of NTD. However, despite the high consumption of bread (the main fortified food with FA) by our population, a high number of pregnant women consume FA supplements, thus, over passing the maximal recommended FA intake. Additionally, if the diet is reduced in vitamin B12, the optimal ratio folates/vit B12 may be altered, thus inducing changes in the methylation of specific genes and other metabolic pathways, affecting fetal development and the long-term health of the neonates. We think that, after 16 years of the initiation of the fortification of wheat flour with FA, it is necessary to evaluate the possible side effects of a high intake of FA in the pregnant population and their offspring. This article shows antecedents about mechanisms of folates and vit B12 at cellular level, and their possible consequences of an elevated FA maternal intake on the offspring.

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“…Folate transfer to the fetus is mediated by the placental transporters folate receptor alpha and beta (FRα/β), proton coupled folate transporter (PCFT) and reduced folate carrier 1 (RFC1) [16,17]. FRα is the main folate transporter responsible for maternal-to-fetal transfer across the placenta (in both mice and humans) and works together with PCFT and RFC1 to control the uptake and release of folate [18][19][20]. PCFT is a high-affinity folate transporter and RFC1 mediates folate transport to the fetus via bi-directional transport [16,19,[21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Although there is limited information on bacterial production of inositol, it is absorbed in the SI [42]. Once absorbed from the maternal gut into the blood, these micronutrients are then transferred transplacentally to the fetus [15,18,43,44].…”

Section: Introductionmentioning

confidence: 99%

Diet alters micronutrient pathways in the gut and placenta that regulate fetal growth and development in pregnant mice

Palladino

Mieghem

Connor

2019

Preprint

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AbstractMaternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems-physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction, or maternal metabolic dysfunction, respectively. At gestational day 18.5 we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundance of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frβ) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα) and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.

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Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

Cited by 24 publications

References 49 publications

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

Folatos y Embarazo, conceptos actuales: ¿Es necesaria una suplementación con Acido Fólico?

Diet alters micronutrient pathways in the gut and placenta that regulate fetal growth and development in pregnant mice

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