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Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation
In the ruminant placenta, glucose uptake and transfer are mediated by facilitative glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). SLC2A1 is located on the basolateral trophoblast membrane, whereas SLC2A3 is located solely on the maternal-facing, apical trophoblast membrane. While SLC2A3 is...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603975/ https://www.ncbi.nlm.nih.gov/pubmed/36293384 http://dx.doi.org/10.3390/ijms232012530 |
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author | Lynch, Cameron S. Kennedy, Victoria C. Tanner, Amelia R. Ali, Asghar Winger, Quinton A. Rozance, Paul J. Anthony, Russell V. |
author_facet | Lynch, Cameron S. Kennedy, Victoria C. Tanner, Amelia R. Ali, Asghar Winger, Quinton A. Rozance, Paul J. Anthony, Russell V. |
author_sort | Lynch, Cameron S. |
collection | PubMed |
description | In the ruminant placenta, glucose uptake and transfer are mediated by facilitative glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). SLC2A1 is located on the basolateral trophoblast membrane, whereas SLC2A3 is located solely on the maternal-facing, apical trophoblast membrane. While SLC2A3 is less abundant than SLC2A1, SLC2A3 has a five-fold greater affinity and transport capacity. Based on its location, SLC2A3 likely plays a significant role in the uptake of glucose into the trophoblast. Fetal hypoglycemia is a hallmark of fetal growth restriction (FGR), and as such, any deficiency in SLC2A3 could impact trophoblast glucose uptake and transfer to the fetus, thus potentially setting the stage for FGR. By utilizing in vivo placenta-specific lentiviral-mediated RNA interference (RNAi) in sheep, we were able to significantly diminish (p ≤ 0.05) placental SLC2A3 concentration, and determine the impact at mid-gestation (75 dGA). In response to SLC2A3 RNAi (n = 6), the fetuses were hypoglycemic (p ≤ 0.05), exhibited reduced fetal growth, including reduced fetal pancreas weight (p ≤ 0.05), which was associated with reduced umbilical artery insulin and glucagon concentrations, when compared to the non-targeting sequence (NTS) RNAi controls (n = 6). By contrast, fetal liver weights were not impacted, nor were umbilical artery concentrations of IGF1, possibly resulting from a 70% increase (p ≤ 0.05) in umbilical vein chorionic somatomammotropin (CSH) concentrations. Thus, during the first half of gestation, a deficiency in SLC2A3 results in fetal hypoglycemia, reduced fetal development, and altered metabolic hormone concentrations. These results suggest that SLC2A3 may be the rate-limiting placental glucose transporter during the first-half of gestation in sheep. |
format | Online Article Text |
id | pubmed-9603975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96039752022-10-27 Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation Lynch, Cameron S. Kennedy, Victoria C. Tanner, Amelia R. Ali, Asghar Winger, Quinton A. Rozance, Paul J. Anthony, Russell V. Int J Mol Sci Article In the ruminant placenta, glucose uptake and transfer are mediated by facilitative glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). SLC2A1 is located on the basolateral trophoblast membrane, whereas SLC2A3 is located solely on the maternal-facing, apical trophoblast membrane. While SLC2A3 is less abundant than SLC2A1, SLC2A3 has a five-fold greater affinity and transport capacity. Based on its location, SLC2A3 likely plays a significant role in the uptake of glucose into the trophoblast. Fetal hypoglycemia is a hallmark of fetal growth restriction (FGR), and as such, any deficiency in SLC2A3 could impact trophoblast glucose uptake and transfer to the fetus, thus potentially setting the stage for FGR. By utilizing in vivo placenta-specific lentiviral-mediated RNA interference (RNAi) in sheep, we were able to significantly diminish (p ≤ 0.05) placental SLC2A3 concentration, and determine the impact at mid-gestation (75 dGA). In response to SLC2A3 RNAi (n = 6), the fetuses were hypoglycemic (p ≤ 0.05), exhibited reduced fetal growth, including reduced fetal pancreas weight (p ≤ 0.05), which was associated with reduced umbilical artery insulin and glucagon concentrations, when compared to the non-targeting sequence (NTS) RNAi controls (n = 6). By contrast, fetal liver weights were not impacted, nor were umbilical artery concentrations of IGF1, possibly resulting from a 70% increase (p ≤ 0.05) in umbilical vein chorionic somatomammotropin (CSH) concentrations. Thus, during the first half of gestation, a deficiency in SLC2A3 results in fetal hypoglycemia, reduced fetal development, and altered metabolic hormone concentrations. These results suggest that SLC2A3 may be the rate-limiting placental glucose transporter during the first-half of gestation in sheep. MDPI 2022-10-19 /pmc/articles/PMC9603975/ /pubmed/36293384 http://dx.doi.org/10.3390/ijms232012530 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lynch, Cameron S. Kennedy, Victoria C. Tanner, Amelia R. Ali, Asghar Winger, Quinton A. Rozance, Paul J. Anthony, Russell V. Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title | Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title_full | Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title_fullStr | Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title_full_unstemmed | Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title_short | Impact of Placental SLC2A3 Deficiency during the First-Half of Gestation |
title_sort | impact of placental slc2a3 deficiency during the first-half of gestation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603975/ https://www.ncbi.nlm.nih.gov/pubmed/36293384 http://dx.doi.org/10.3390/ijms232012530 |
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