Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction

McIntyre, K. R. , Vincent, K. M. M., Hayward, C. E., Li, X., Sibley, C. P., Desforges, M., Greenwood, S. L. and Dilworth, M. R. (2020) Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction. Scientific Reports, 10, 16197. (doi: 10.1038/s41598-020-72930-7) (PMID:33004923) (PMCID:PMC7530652)

Abstract

Fetal growth restriction (FGR) is a significant risk factor for stillbirth, neonatal complications and adulthood morbidity. Compared with those of appropriate weight for gestational age (AGA), FGR babies have smaller placentas with reduced activity of amino acid transporter systems A and L, thought to contribute to poor fetal growth. The amino acids glutamine and glutamate are essential for normal placental function and fetal development; whether transport of these is altered in FGR is unknown. We hypothesised that FGR is associated with reduced placental glutamine and glutamate transporter activity and expression, and propose the mammalian target of rapamycin (mTOR) signaling pathway as a candidate mechanism. FGR infants [individualised birth weight ratio (IBR) < 5th centile] had lighter placentas, reduced initial rate uptake of 14C-glutamine and 14C-glutamate (per mg placental protein) but higher expression of key transporter proteins (glutamine: LAT1, LAT2, SNAT5, glutamate: EAAT1) versus AGA [IBR 20th–80th]. In further experiments, in vitro exposure to rapamycin inhibited placental glutamine and glutamate uptake (24 h, uncomplicated pregnancies) indicating a role of mTOR in regulating placental transport of these amino acids. These data support our hypothesis and suggest that abnormal glutamine and glutamate transporter activity is part of the spectrum of placental dysfunction in FGR.

• Item Type: Articles
• Additional Information: K.R.M. conducted this work during her PhD studentship, which was supported by a Medical Research Council Doctoral Training Partnership (1 512 341). This work was also supported by a Career Development Fellowship Award from the Medical Research Council (MR/K024442/1) awarded to M.R.D. The National Institute for Health Research Manchester Biomedical Research Centre and Tommy’s charity provided infrastructure support.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McIntyre, Dr Kirsty
• Authors: McIntyre, K. R., Vincent, K. M. M., Hayward, C. E., Li, X., Sibley, C. P., Desforges, M., Greenwood, S. L., and Dilworth, M. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Scientific Reports 10:16197
• Publisher Policy: Reproduced under a Creative Commons License