Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction

McIntyre, K. R. , Hayward, C. E., Sibley, C. P., Greenwood, S. L. and Dilworth, M. R. (2019) Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction. Journal of Physiology, 597(19), pp. 4975-4990. (doi: 10.1113/jp278226) (PMID:31400764) (PMCID:PMC6790568)

Abstract

Fetal growth restriction (FGR), a major risk factor for stillbirth, and neonatal and adulthood morbidity, is associated with reduced placental size and decreased placental nutrient transport. In mice, a small, normal placenta increases its nutrient transport, thus compensating for its reduced size and maintaining normal fetal growth. Whether this adaptation occurs for glutamine and glutamate, two key amino acids for placental metabolism and fetal growth, is unknown. Additionally, an assessment of placental transport of glutamine and glutamate between FGR and normal pregnancy is currently lacking. We thus tested the hypothesis that the transport of glutamine and glutamate would be increased (per gram of tissue) in a small normal placenta [C57BL6/J (wild‐type, WT) mice], but that this adaptation fails in the small dysfunctional placenta in FGR [insulin‐like growth factor 2 knockout (P0) mouse model of FGR]. In WT mice, comparing the lightest versus heaviest placenta in a litter, unidirectional maternofetal clearance (Kmf) of 14C‐glutamine and 14C‐glutamate (glutamineKmf and glutamateKmf) was significantly higher at embryonic day (E) 18.5, in line with increased expression of LAT1, a glutamine transporter protein. In P0 mice, glutamineKmf and glutamateKmf were higher (P0 versus wild‐type littermates, WTL) at E15.5. At E18.5, glutamineKmf remained elevated whereas glutamateKmf was similar between groups. In summary, we provide evidence that glutamineKmf and glutamateKmf adapt according to placental size in WT mice. The placenta of the growth‐restricted P0 fetus also elevates transport capacity to compensate for size at E15.5, but this adaptation is insufficient at E18.5; this may contribute to decreased fetal growth.

• Item Type: Articles
• Additional Information: The work herein was supported by a Career Development Fellowship Award from the Medical Research Council (MR/K024442/1) awarded to M.R.D. and a Medical Research Council Doctoral Training Partnership PhD studentship (1 512 341) awarded to K.R.M.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McIntyre, Dr Kirsty
• Authors: McIntyre, K. R., Hayward, C. E., Sibley, C. P., Greenwood, S. L., and Dilworth, M. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Physiology
• Publisher: Wiley
• ISSN: 0022-3751
• ISSN (Online): 1469-7793
• Published Online: 10 August 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Journal of Physiology 597(19): 4975-4990
• Publisher Policy: Reproduced under a Creative Commons License