Gestational diabetic transcriptomic profiling of microdissected human trophoblast

Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is influenced by the placenta, and its prevalence directly increases with obesity. Therefore, to define the aetiology of GDM requires that the confounding influence of obesity and the heterogeneous nature of th...

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Main Authors: Bari, M, Ngo, S, Bastie, C, Sheppard, A, Vatish, M
Format: Journal article
Language:English
Published: BioScientifica 2016
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author Bari, M
Ngo, S
Bastie, C
Sheppard, A
Vatish, M
author_facet Bari, M
Ngo, S
Bastie, C
Sheppard, A
Vatish, M
author_sort Bari, M
collection OXFORD
description Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is influenced by the placenta, and its prevalence directly increases with obesity. Therefore, to define the aetiology of GDM requires that the confounding influence of obesity and the heterogeneous nature of the placenta impairing accurate quantitative studies be accounted for. Using laser capture microdissection (LCM), we optimized RNA extraction from human placental trophoblast, the metabolic cellular interface between mother and foetus. This allowed specific transcriptomic profiling of trophoblast isolated from GDM, and obese and normal human placentae. Genome-wide gene expression analysis was performed on the RNA extracted from the trophoblast of GDM and obese and normal placentae. Forty-five differentially expressed genes (DEGs) specifically discriminated GDM from matched obese subjects. Two genes previously linked with GDM, pregnancy specific beta-1 glycoprotein 6 (PSG6) and placental system A sodium-dependent transporter system (SLC38A1), were significantly increased in GDM. A number of these DEGs (8 ubiquitin-conjugating enzymes (UBE) splice variants (UBE2D3 variants 1, 3, 4, 5, 6, 7, and 9) and UBE2V1 variant 4)) were involved in RNA processing and splicing, and a significant number of the DEGs, including the UBE variants, were associated with increased maternal fasting plasma glucose.It is concluded that DEGs discriminating GDM from obese subjects were pinpointed. Our data indicate a biological link between genes involved in RNA processing and splicing, ubiquitination, and fasting plasma glucose in GDM taking into account obesity as the confounder.
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spelling oxford-uuid:9f693f1a-71e5-4c49-bef1-03b2ac2bc0272022-03-27T00:57:32ZGestational diabetic transcriptomic profiling of microdissected human trophoblastJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9f693f1a-71e5-4c49-bef1-03b2ac2bc027EnglishSymplectic Elements at OxfordBioScientifica2016Bari, MNgo, SBastie, CSheppard, AVatish, MGestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is influenced by the placenta, and its prevalence directly increases with obesity. Therefore, to define the aetiology of GDM requires that the confounding influence of obesity and the heterogeneous nature of the placenta impairing accurate quantitative studies be accounted for. Using laser capture microdissection (LCM), we optimized RNA extraction from human placental trophoblast, the metabolic cellular interface between mother and foetus. This allowed specific transcriptomic profiling of trophoblast isolated from GDM, and obese and normal human placentae. Genome-wide gene expression analysis was performed on the RNA extracted from the trophoblast of GDM and obese and normal placentae. Forty-five differentially expressed genes (DEGs) specifically discriminated GDM from matched obese subjects. Two genes previously linked with GDM, pregnancy specific beta-1 glycoprotein 6 (PSG6) and placental system A sodium-dependent transporter system (SLC38A1), were significantly increased in GDM. A number of these DEGs (8 ubiquitin-conjugating enzymes (UBE) splice variants (UBE2D3 variants 1, 3, 4, 5, 6, 7, and 9) and UBE2V1 variant 4)) were involved in RNA processing and splicing, and a significant number of the DEGs, including the UBE variants, were associated with increased maternal fasting plasma glucose.It is concluded that DEGs discriminating GDM from obese subjects were pinpointed. Our data indicate a biological link between genes involved in RNA processing and splicing, ubiquitination, and fasting plasma glucose in GDM taking into account obesity as the confounder.
spellingShingle Bari, M
Ngo, S
Bastie, C
Sheppard, A
Vatish, M
Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title_full Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title_fullStr Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title_full_unstemmed Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title_short Gestational diabetic transcriptomic profiling of microdissected human trophoblast
title_sort gestational diabetic transcriptomic profiling of microdissected human trophoblast
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AT ngos gestationaldiabetictranscriptomicprofilingofmicrodissectedhumantrophoblast
AT bastiec gestationaldiabetictranscriptomicprofilingofmicrodissectedhumantrophoblast
AT shepparda gestationaldiabetictranscriptomicprofilingofmicrodissectedhumantrophoblast
AT vatishm gestationaldiabetictranscriptomicprofilingofmicrodissectedhumantrophoblast