Disparity Between Placental Glutamine and Glutamate Transporter Activity and Expression in Fetal Growth Restriction

McIntyre, K. , Hayward, C., Sibley, C., Greenwood, S. and Dilworth, M. (2018) Disparity Between Placental Glutamine and Glutamate Transporter Activity and Expression in Fetal Growth Restriction. 65th Annual Meeting of the Society for Reproductive Investigation (SRI), San Diego, CA, USA, 06-10 Mar 2018.

Abstract

Introduction: Fetal growth restriction (FGR) is a significant clinical problem, affecting between 5-10% of pregnancies, yet no treatment options currently exist. Addressing this requires improved understanding of the relationship between placental nutrient transport and fetal growth. Glutamine (transported by systems A, L and N) and glutamate (transported by system XAG-) are important amino acids for fetal growth and metabolism. We tested the hypothesis that the activity and expression of glutamine and glutamate transporters is lower in placentas from FGR babies compared to placentas of babies appropriately grown for gestational age (AGA). Methods: Placental villous fragments from AGA (n=18/19, individualised birthweight centile (IBR)13.6-87.7, gestation 260-282 days) and FGR (n=10/11, IBR 0-3.5, gestation 205-284 days) babies were exposed to 14C-glutamine or 14C-glutamate. The initial rate of transporter-mediated uptake of radiolabelled amino acids was measured over 30-90min and expressed in pmol/mg protein. The expression of glutamine (LAT1, LAT2, SNAT5) and glutamate (EAAT1, EAAT2) transporter proteins were assessed by Western blot of membrane-enriched placental tissue. Results: Placental weight was significantly lower in FGR compared to AGA babies (p<0.001; Mann Whitney). In FGR versus AGA babies, uptake of 14C-glutamine (p=0.08, linear regression) and 14C-glutamate (p=0.16) was similar between groups. Relative to B-tubulin, placental expression of LAT1, LAT2 and SNAT5 (p<0.05; Mann Whitney) and EAAT1 (p<0.001) but not EAAT2, was significantly higher in FGR versus AGA. Conclusion: Placental expression of proteins important for glutamine (LAT1, LAT2, SNAT5) and glutamate (EAAT1) transport was higher in FGR compared with AGA babies. This may be an adaptive response, which ensures appropriate glutamine and glutamate uptake into the placenta (per mg protein). However, these data should be considered in the context of the reduced placental size in FGR which would likely lead to reduced overall placental accumulation, and thus fetal delivery, of amino acids to the growth restricted fetus.

• Item Type: Conference or Workshop Item
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McIntyre, Dr Kirsty
• Authors: McIntyre, K., Hayward, C., Sibley, C., Greenwood, S., and Dilworth, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing