Down-regulation of placental folate transporters in intrauterine growth restriction |
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| Institution: | 1. Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus Aurora, CO, USA;2. Division of High-risk Pregnancy, Department of Obstetrics & Gynecology, Mackay Memorial Hospital, Taipei, Taiwan;3. Children''s Health Research Institute, University of Western Ontario, London, ON, Canada;4. Department of Pediatrics and Biochemistry, University of Western Ontario, London, ON, Canada;5. Department of Obstetrics and Gynecology, University of Western Ontario, London, ON, Canada;6. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;1. Depto. de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Ciudad de México, Mexico;2. Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico;1. Military Performance Division, United States Army Research Institute of Environmental Medicine, Natick, MA, 01760;2. Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, 01760;1. Department of Clinical Pharmacy, USC School of Pharmacy, Los Angeles, CA 90033, USA;2. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy;3. Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA;1. Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202;2. Department of Nutrition and Food Sciences, Texas A&M University, College Station, TX 77843;3. Department of Pathology, University of North Dakota, Grand Forks, ND 58202;4. ND-INBRE Bioinfomatic Core, University of North Dakota, Grand Forks, ND 58202;5. Hubei Cancer Hospital, Wuhan, Hubei 430079, China;6. Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;7. Campus Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China;8. Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA;9. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA;10. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA |
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| 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 weight 1804±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. |
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