Abstract
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.
Highlights
Folates are water-soluble vitamins of the B complex that are naturally present in foods as reduced forms or glutamate chains
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, with differences mainly related to their location within the placenta (BP and CP)
FOLR1 protein concentrations were higher in preterm births (PT) than in term placentas, justifying the higher concentrations of folate found in cord blood of PT newborns
Summary
Folates are water-soluble vitamins of the B complex that are naturally present in foods as reduced forms or glutamate chains. Chile started FA fortification in 2001 with 2.4 mg of FA/1000 g in wheat flour [10], which led to a 43% decrease in the prevalence of NTD two years later [11] This greater supply of FA along with the greater bioavailability of FA (near 100%), twice that of natural folate [4], have dramatically increased FA consumption levels with unknown long-term effects on offspring. Vitamin B12, which is present mainly in foods of animal origin [14], is essential during pregnancy due to its role in folate metabolism, normal cell growth, prevention of birth defects and neurocognitive development [15,16]. The maternal requirement of vitamin B12 during pregnancy is slightly higher than in adults (from 2.4 to 2.6 μg/day) [4]
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