Obese women have an approximately twofold higher risk to deliver an infant with neural tube defects (NTDs) despite folate supplementation. Placental transfer of folate is mediated by folate receptor alpha (FR-α), proton coupled folate transporter (PCFT), and reduced folate carrier (RFC). Decreased placental transport may contribute to NTDs in obese women. Serum folate levels were measured and placental tissue was collected from 13 women with normal BMI (21.9±1.9) and 11 obese women (BMI 33.1±2.8) undergoing elective termination at 8–22 weeks of gestation. 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 capacity was assessed using radiolabeled methyl-tetrahydrofolate and rapid filtration techniques. Differences in expression and transport capacity were adjusted for gestational age and maternal age in multivariable regression models. P<.05 was considered statistically significant. Serum folate levels were not significantly different between groups. Placental MVM folate transporter expression did not change with gestational age. MVM RFC (−19%) and FR-α (−17%) expression was significantly reduced in placentas from obese women (P<.05). MVM folate transporter activity was reduced by−52% (P<.05) in obese women. These differences remained after adjustment for gestational age. There was no difference in mTOR signaling between groups. In conclusion, RFC and FR alpha expression and transporter activity in the placental MVM are significantly reduced in obese women in early pregnancy. These results may explain the higher incidence of NTDs in infants of obese women with adequate serum folate.

尽管补充叶酸，肥胖妇女的分娩婴儿神经管缺陷（NTDs）的风险大约高出两倍。叶酸的胎盘转移是由叶酸受体α（FR-α），质子偶联的叶酸转运蛋白（PCFT）和还原的叶酸载体（RFC）介导的。胎盘运输减少可能会导致肥胖妇女的NTD。测量了血清叶酸水平，并从13名BMI正常的妇女（21.9±1.9）和11名肥胖妇女（BMI 33.1±2.8）在妊娠8-22周时进行了择期终止，收集了胎盘组织。使用匀浆，镁沉淀和差速离心分离合体滋养层微孔质膜（MVM）。通过蛋白质印迹法测定FR-α，PCFT和RFC的MVM表达。使用放射性标记的四氢叶酸甲酯和快速过滤技术评估叶酸的运输能力。在多变量回归模型中，针对胎龄和产妇年龄调整了表达和转运能力的差异。P <.05被认为具有统计学意义。两组之间的血清叶酸水平无显着差异。胎盘MVM叶酸转运蛋白的表达并没有随着胎龄的变化而变化。肥胖妇女胎盘中的MVM RFC（−19％）和FR-α（−17％）表达显着降低（P <.05）。肥胖女性的MVM叶酸转运蛋白活性降低了-52％（P <.05）。调整胎龄后，这些差异仍然存在。两组之间的mTOR信号没有差异。总而言之，肥胖和妊娠早期肥胖妇女的胎盘MVM中RFC和FR alpha表达以及转运蛋白活性显着降低。这些结果可能解释了患有充足血清叶酸的肥胖妇女婴儿中NTD的发生率较高。