A systems perspective on placental amino acid transport

Cleal, Jane K.; Lofthouse, Emma M.; Sengers, Bram G.; Lewis, Rohan M.

doi:10.1113/jp274883

Cited by 56 publications

(65 citation statements)

References 58 publications

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“…In all cases where K mf is used to assess amino acid transfer across the placenta in mice, it is possible that the time taken for the radiolabelled isotopes to equilibrate with intracellular metabolic compartments/amino acid pools that exist within the placenta (Velázquez et al 1976;Day et al 2013;Cleal et al 2018) could underestimate the true clearance over the time course of the experiment.…”

Section: Discussionmentioning

confidence: 99%

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

McIntyre

Hayward

Sibley

et al. 2019

The Journal of Physiology

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Key points Fetal growth restriction (FGR) is a major risk factor for stillbirth and has significant impact upon lifelong health. A small, poorly functioning placenta, as evidenced by reduced transport of nutrients to the baby, underpins FGR. It remains unclear how a small but normal placenta differs from the small FGR placenta in terms of ability to transfer nutrients to the fetus. Placental transport of glutamine and glutamate, key amino acids for fetal growth, was assessed in normal mice and those with FGR. Glutamine and glutamate transport was greater in the lightest versus heaviest placenta in a litter of normally grown mice. Placentas of mice with FGR had increased transport capacity in mid‐pregnancy, but this adaptation was insufficient in late pregnancy. Placental adaptations, in terms of increased nutrient transport (per gram) to compensate for small size, appear to achieve appropriate fetal growth in normal pregnancy. Failure of this adaptation might contribute to FGR. 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.

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Section: Discussionmentioning

confidence: 99%

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

McIntyre

Hayward

Sibley

et al. 2019

The Journal of Physiology

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“…A common design strategy for AA transport in epithelial cells of the gut (7,8), placenta (11), and kidney (29) is functional cooperation between concentrative and dissipative transport systems by means of AA gradient coupling. In the colonocyte, outward AA gradients created by concentrative AA transporters in the apical membrane (SLC1A1, -1A5, -6A6, -6A14, -6A15, and -38A1) and basolateral membrane (SLC1A4, -6A9, -7A6, -38A2, and -38A3) could be harnessed by AA exchangers (SLC1A5, -1A4, -7A5, and -7A6) to the uptake of other extracellular AAs.…”

Section: A R G + a S N A S P -G L U -L Y S + M E T P H E G L N I L E mentioning

confidence: 99%

Absorptive transport of amino acids by the rat colon

Chen

Dinges

Green

et al. 2020

American Journal of Physiology-Gastrointestinal and Liver Physi

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The capacity of the colon to absorb microbially produced amino acids (AAs) and the underlying mechanisms of AA transport are incompletely defined. We measured the profile of 16 fecal AAs along the rat ceco-colonic axis and compared unidirectional absorptive AA fluxes across mucosal tissues isolated from the rat jejunum, cecum, and proximal colon using an Ussing chamber approach, in conjunction with 1H-NMR and ultra-performance liquid chromatography-mass spectrometry chemical analyses. Passage of stool from cecum to midcolon was associated with segment-specific changes in fecal AA composition and a decrease in total AA content. Simultaneous measurement of up to 16 AA fluxes under native luminal conditions, with correction for endogenous AA release, demonstrated absorptive transfer of AAs across the cecum and proximal colon at rates comparable (30–80%) to those across the jejunum, with significant Na+-dependent and H+-stimulated components. Expression profiling of 30 major AA transporter genes by quantitative PCR revealed comparatively high levels of transcripts for 20 AA transporters in the cecum and/or colon, with the levels of 12 exceeding those in the small intestine. Our results suggest a more detailed model of major apical and basolateral AA transporters in rat colonocytes and provide evidence for a previously unappreciated transfer of AAs across the colonic epithelium that could link the prodigious metabolic capacities of the luminal microbiota, the colonocytes, and the body tissues. NEW & NOTEWORTHY This study provides evidence for a previously unappreciated transfer of microbially generated amino acids across the colonic epithelium under physiological conditions that could link the prodigious metabolic capacities of the luminal microbiota, the colonocytes, and the body tissues. The segment-specific expression of at least 20 amino acid transporter genes along the colon provides a detailed mechanistic basis for uniport, heteroexchange, Na+-cotransport, and H+-cotransport components of colonic amino acid absorption.

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“…Transport by active transport through accumulative transporters and exchangers on the MVM and BM (Figure 3). Accumulative transporters generally increase intracellular concentrations of amino acids by mediating uptake often by co-transporting extracellular sodium [86]. Exchangers alter amino acid concentrations by swapping amino acids between intracellular and extracellular compartments.…”

Section: Amino Acidsmentioning

confidence: 99%

The impact of maternal obesity in pregnancy on placental glucocorticoid and macronutrient transport and metabolism

Johns

Denison

Reynolds

2020

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Maternal obesity is the most common metabolic disturbance in pregnancy affecting more than 1 in 5 women in some countries. Babies born to obese women are heavier with more adiposity at birth, and are vulnerable to obesity and metabolic disease across the lifespan suggesting offspring health is 'programmed' by fetal exposure to an obese intra-uterine environment. The placenta plays a major role in dictating the impact of maternal health on prenatal development. Maternal obesity impacts the function of integral placental receptors and transporters for glucocorticoids and nutrients, key drivers of fetal growth, though mechanisms remain poorly understood. This review aims to summarise current knowledge in this area, and considers the impact of obesity on the epigenetic machinery of the placenta at this vital juncture in offspring development. Further research is required to advance understanding of these areas in the hope that the trans-generational cycle of obesity can be alleviated.

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A systems perspective on placental amino acid transport

Cited by 56 publications

References 58 publications

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

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

Absorptive transport of amino acids by the rat colon

The impact of maternal obesity in pregnancy on placental glucocorticoid and macronutrient transport and metabolism

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