Down-regulation of placental folate transporters in intrauterine growth restriction.

Authors

Yi-Yung Chen, University of ColoradoFollow
Madhulika B Gupta, Western UniversityFollow
Rob Grattton, Western UniversityFollow
Theresa L Powell, University of ColoradoFollow
Thomas Jansson, University of ColoradoFollow

Document Type

Article

Publication Date

9-1-2018

Journal

The Journal of Nutritional Biochemistry

Volume

59

First Page

136

Last Page

141

URL with Digital Object Identifier

https://doi.org/10.1016/j.jnutbio.2018.06.003

Abstract

Folate deficiency in pregnancy is associated with neural tube defects, restricted fetal growth and fetal programming of diseases later in life. Fetal folate availability is dependent on maternal folate levels and placental folate transport capacity, mediated by two key transporters, Folate Receptor-α and Reduced Folate Carrier(RFC). We tested the hypothesis that intrauterine growth restriction (IUGR) is associated with decreased folate transporter expression and activity in isolated syncytiotrophoblast microvillous plasma membranes (MVM). Women with pregnancies complicated by IUGR (birth weight <3rd percentile, mean birth weight1804±110 g, gestational age 35.7±0.61 weeks, n=25) and women delivering an appropriately-for gestational age infant (control group, birth weight 25th–75th centile, mean birth weight 2493±216 g, gestational age 33.9±0.95 weeks, n=19) were recruited and placentas were collected at delivery. MVM was isolated and folate transporter protein expression was measured using Western blot and transporter activity was determined using radiolabelled methyltetrahydrofolic acid and rapid filtration. Whereas the expression of FR-α was unaffected, MVM RFC protein expression was significantly decreased in the IUGR group (−34%, P<.05). IUGR MVM had a significantly lower folate uptake compared to the control group (−38%, P<.05). In conclusion, placental folate transport capacity is decreased in IUGR, which may contribute to the restricted fetal growth and intrauterine programming of childhood and adult disease. These findings suggest that continuation of folate supplementation in the second and third trimester is of particular importance in pregnancies complicated by IUGR.

Notes

Article available at The Journal of Nutritional Biochemistry

https://doi.org/10.1016/j.jnutbio.2018.06.003