Relationship between folate transporters expression in human placentas at term and birth weights

Caviedes, Lorena; Íñiguez, Germán; Hidalgo, Paulina; Castro, Juan Jose; Castaño, Erika; Llanos, Miguel; Hirsch, Sandra; Ronco, Ana María

doi:10.1016/j.placenta.2015.12.007

Cited by 18 publications

(17 citation statements)

References 32 publications

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“…Similar changes were observed in placentas of term pregnancies with newborns of different birth weight, as recently reported by us [30]. Preterm placentas had lower FOLR1 mRNA than controls, likely due to a negative feedback on the folr1 gene to prevent further folate transfer to the fetus.…”

Section: Discussionsupporting

confidence: 87%

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

et al. 2017

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Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32–36 weeks, n = 51). Term placentas were used as controls (T, 37–41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

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Section: Discussionsupporting

confidence: 87%

“…Results were expressed in relation to the geometric mean expression of three of the most stable housekeeping genes (GAPDH, YWHAZ and β-actin) [29], using the term group as control. Gene primers were described previously [30]. Life Technologies supplied Primers for FOLR1 (assay code: Hs01124177_m1).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…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 . These results suggest that there is an interaction between folates and vit B12 that is related to gestational age and to birth weight.…”

Section: Transport Of Folate To the Fetusmentioning

confidence: 64%

“…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%

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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“…Raised mRNA abundance of FOLR1, if translated to protein, and accompanied with a decline in maternal folate concentration would result in the maintenance of cord blood folate as we observed at term with obesity. Alternatively mRNA transcripts of this folate transporter could undergo further functional modifications, that modulate the placentas capacity to promote folate transport [ 31 ] and, hence, protect normal foetal folate status as seen in women from Texas, USA [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta

et al. 2018

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Dietary methyl donors, including folate, may modify the placenta and size at birth but the influence of maternal body weight has not been widely investigated. We therefore examined whether maternal or fetal folate status, together with indices of placental folate transport, were modulated by either maternal pre-pregnancy body mass index (BMI i.e., overweight: 25 ≤ BMI < 30 or obesity: BMI ≥ 30 kg/m2) and/or gestational diabetes mellitus (GD). We utilised a sub-sample of 135 pregnant women participating in the Spanish PREOBE survey for our analysis (i.e., 59 healthy normal weight, 29 overweight, 22 obese and 25 GD). They were blood sampled at 34 weeks gestation, and, at delivery, when a placental sample was taken together with maternal and cord blood. Placental gene expression of folate transporters and DNA methyltransferases (DNMT) were all measured. Folate plasma concentrations were determined with an electro-chemiluminescence immunoassay. Food diaries indicated that folate intake was unaffected by BMI or GD and, although all women maintained normal folate concentrations (i.e., 5–16 ng/mL), higher BMIs were associated with reduced maternal folate concentrations at delivery. Umbilical cord folate was not different, reflecting an increased concentration gradient between the mother and her fetus. Placental mRNA abundance for the folate receptor alpha (FOLR1) was reduced with obesity, whilst DNMT1 was increased with raised BMI, responses that were unaffected by GD. Multi-regression analysis to determine the best predictors for placental FOLR1 indicated that pre-gestational BMI had the greatest influence. In conclusion, the placenta’s capacity to maintain fetal folate supply was not compromised by either obesity or GD.

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Relationship between folate transporters expression in human placentas at term and birth weights

Cited by 18 publications

References 32 publications

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

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

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

The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta

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