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

Date Published: January 19, 2017

Publisher: Public Library of Science

Author(s): Erika Castaño, Lorena Caviedes, Sandra Hirsch, Miguel Llanos, Germán Iñiguez, Ana María Ronco, Colette Kanellopoulos-Langevin.


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.

Partial Text

Folates are water-soluble vitamins of the B complex that are naturally present in foods as reduced forms or glutamate chains. The synthetic form, folic acid (FA), is fully oxidized and more stable; it is frequently used in fortified foods or as supplements [1,2]. Folates are needed for fetal growth and placental development, since they activate cell growth and biosynthetic processes that are essential during pregnancy [3]. For these reasons maternal requirements during pregnancy are 50% greater than adult requirements (400 μg/day) [3,4].

In this study we present results indicating that mRNA and protein levels of folate transporters are different in placental tissue of preterm compared to those of term newborns (control), with differences mainly related to their location within the placenta (BP and CP). 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. In addition, FOLR1 mRNA correlated positively with gestational age. By contrast, FOLR1 protein concentrations were higher in PT than in term placentas, justifying the higher concentrations of folate found in cord blood of PT newborns. In addition, PT newborns had lower vitamin B12 concentrations in cord blood than those found in term newborns.




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