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胎盘营养转运体在大鼠持续性母体低血糖中发生适应性改变。

Placental nutrient transporters adapt during persistent maternal hypoglycaemia in rats.

机构信息

Department of Safety Sciences, Imaging & Data Management, Novo Nordisk A/S, Maaloev, Denmark.

Department of Pediatrics, Medical Faculty, University of Cologne, Cologne, Germany.

出版信息

PLoS One. 2022 Mar 28;17(3):e0265988. doi: 10.1371/journal.pone.0265988. eCollection 2022.

DOI:10.1371/journal.pone.0265988
PMID:35344549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8959168/
Abstract

Maternal malnutrition is associated with decreased nutrient transfer to the foetus, which may lead to foetal growth restriction, predisposing children to a variety of diseases. However, regulation of placental nutrient transfer during decreased nutrient availability is not fully understood. In the present study, the aim was to investigate changes in levels of placental nutrient transporters accompanying maternal hypoglycaemia following different durations and stages of gestation in rats. Maternal hypoglycaemia was induced by insulin-infusion throughout gestation until gestation day (GD)20 or until end of organogenesis (GD17), with sacrifice on GD17 or GD20. Protein levels of placental glucose transporters GLUT1 (45/55 kDa isotypes) and GLUT3, amino acid transporters SNAT1 and SNAT2, and insulin receptor (InsR) were assessed. On GD17, GLUT1-45, GLUT3, and SNAT1 levels were increased and InsR levels decreased versus controls. On GD20, following hypoglycaemia throughout gestation, GLUT3 levels were increased, GLUT1-55 showed the same trend. After cessation of hypoglycaemia at end of organogenesis, GLUT1-55, GLUT3, and InsR levels were increased versus controls, whereas SNAT1 levels were decreased. The increases in levels of placental nutrient transporters seen during maternal hypoglycaemia and hyperinsulinemia likely reflect an adaptive response to optimise foetal nutrient supply and development during limited availability of glucose.

摘要

母体营养不良与向胎儿传递的营养物质减少有关,这可能导致胎儿生长受限,使儿童易患多种疾病。然而,在营养物质供应减少的情况下,胎盘营养物质转运的调节机制尚未完全阐明。本研究旨在探讨母体低血糖症伴随不同孕期和妊娠期阶段对大鼠胎盘营养转运体水平的影响。通过在整个妊娠期直至妊娠第 20 天(GD20)或直至器官发生结束(GD17)期间输注胰岛素诱导母体低血糖症,然后在 GD17 或 GD20 处死。评估胎盘葡萄糖转运体 GLUT1(45/55 kDa 同工型)和 GLUT3、氨基酸转运体 SNAT1 和 SNAT2 以及胰岛素受体(InsR)的蛋白水平。在 GD17 时,与对照组相比,GLUT1-45、GLUT3 和 SNAT1 水平增加,InsR 水平降低。在整个妊娠期发生低血糖症后,GD20 时 GLUT3 水平增加,GLUT1-55 呈相同趋势。在器官发生结束时停止低血糖症后,与对照组相比,GLUT1-55、GLUT3 和 InsR 水平增加,而 SNAT1 水平降低。母体低血糖症和高胰岛素血症期间观察到的胎盘营养转运体水平升高可能反映了一种适应性反应,以优化胎儿在葡萄糖有限供应期间的营养供应和发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/580bf5a89f90/pone.0265988.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/1dadc07aae15/pone.0265988.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/8906658a55fe/pone.0265988.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/e6242098ed24/pone.0265988.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/c1ed52c30322/pone.0265988.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/9b45c6eb7b8e/pone.0265988.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/580bf5a89f90/pone.0265988.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/1dadc07aae15/pone.0265988.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/8906658a55fe/pone.0265988.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/e6242098ed24/pone.0265988.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/c1ed52c30322/pone.0265988.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/9b45c6eb7b8e/pone.0265988.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/746f/8959168/580bf5a89f90/pone.0265988.g006.jpg

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本文引用的文献

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Importance of gestational hypoglycaemia for foetal malformations and skeletal development in rats.妊娠低血糖症对大鼠胎儿畸形和骨骼发育的重要性。
Reprod Toxicol. 2020 Jan;91:14-26. doi: 10.1016/j.reprotox.2019.10.003. Epub 2019 Oct 20.
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Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact.
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Effect of maternal hypoglycaemia during gestation on materno-foetal nutrient transfer and embryo-foetal development: Evidence from experimental studies focused primarily on the rat.妊娠期间母体低血糖对母婴营养转移和胚胎-胎儿发育的影响:主要来自于大鼠的实验研究证据。
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