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Neural tube defects (NTDs) are one of the most common birth defects worldwide and represent a major cause of disability. Obese women have two fold higher risk for NTDs, which appear to be resistant to folate supplementation. Placental transfer of folate is mediated by three proteins; folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport capacity may contribute to NTDs in women with normal folate levels. We tested the hypothesis that early pregnancy placental folate transport capacity is reduced in obese women.
Placental tissue was collected from 13 women with normal BMI (21.9 ± 1.9), mean gestational age 14.3 weeks and 11 obese women (33.1 ± 2.8), mean gestational age 15.6 weeks, who were undergoing elective termination of pregnancy. The syncytiotrophoblast microvillous plasma membranes (MVM) were isolated using homogenization, magnesium precipitation, and differential centrifugation. MVM expression of FR-α, PCFT and RFC was determined by western blot. Folate transport was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. We measured serum folate levels in both groups of women. Statistical differences were evaluated by student’s t test with significance of p ≤ 0.05.
Serum folate levels were not significantly different in normal and obese women. Placental MVM folate transporter expression did not change significantly with gestational age (range 8-22 wks). Expression of PCFT was not altered by maternal BMI. Placental expression of RFC (-19%) and FR-α (-17%) was significantly decreased in obese women as compared to normal BMI women (p < 0.05). Additionally, folate placental transporter activity was reduced by 52% (p<0.05) in obese compared to normal women (Figure 1).
Folate transporter expression and activity in the placental MVM is reduced in obese women in early pregnancy. This decrease would impair placental folate transfer to the fetus and could result in fetal folate deficiency. These results may explain the higher incidence of NTDs in fetuses of obese women despite adequate maternal folate levels.