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Status |
Public on Apr 26, 2024 |
Title |
Fetal Hypoglycemia Induced by Placental SLC2A3 RNA Inter-ference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation |
Organism |
Ovis aries |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facili-tative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypo-glycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, partic-ularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling, including PPAR and PI3K-Akt signaling, as well as negative regulation of cellular proliferation were also impacted. A few genes directly related to gluconeogenesis were also dif-ferentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to beta cell function.
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Overall design |
To investigate the impact of placental SLC2A3 deficiency, we performed a transcriptomic analysis on fetal pancreases at mid-gestation.
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Contributor(s) |
Kennedy VC, Lynch CS, Tanner AR, Winger QA, Gad A, Rozance PJ, Anthony RV |
Citation missing |
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Submission date |
Mar 19, 2024 |
Last update date |
Apr 26, 2024 |
Contact name |
Victoria Kennedy |
E-mail(s) |
Tori.Kennedy@colostate.edu
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Organization name |
Colorado State University
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Street address |
1683 Campus Delivery
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City |
Fort Collins |
State/province |
Colorado |
ZIP/Postal code |
80523-1683 |
Country |
USA |
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Platforms (1) |
GPL27721 |
Illumina NovaSeq 6000 (Ovis aries) |
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Samples (8)
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GSM8154775 |
fetal pancreas, sample #2, ewe#221, 472-RNAi |
GSM8154776 |
fetal pancreas,sample #3, ewe#336, 472-RNAi |
GSM8154777 |
fetal pancreas,sample #5, ewe#317, 472-RNAi |
GSM8154778 |
fetal pancreas,sample #6, ewe#215, 472-RNAi |
GSM8154779 |
fetal pancreas,sample #7, ewe#263, NTS-RNAi |
GSM8154780 |
fetal pancreas,sample #8, ewe#323, NTS-RNAi |
GSM8154781 |
fetal pancreas,sample #11, ewe#328, NTS-RNAi |
GSM8154782 |
fetal pancreas, sample #12,ewe#333, NTS-RNAi |
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Relations |
BioProject |
PRJNA1089605 |
Supplementary file |
Size |
Download |
File type/resource |
GSE261932_fetal_pancreas_genes_TPM.xlsx |
4.0 Mb |
(ftp)(http) |
XLSX |
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