Cargando…

Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women

An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in n...

Descripción completa

Detalles Bibliográficos
Autores principales: Sharp, Gemma C., Hutchinson, James L., Hibbert, Nanette, Freeman, Tom C., Saunders, Philippa T. K., Norman, Jane E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866706/
https://www.ncbi.nlm.nih.gov/pubmed/27176052
http://dx.doi.org/10.1371/journal.pone.0155413
_version_ 1782431953445715968
author Sharp, Gemma C.
Hutchinson, James L.
Hibbert, Nanette
Freeman, Tom C.
Saunders, Philippa T. K.
Norman, Jane E.
author_facet Sharp, Gemma C.
Hutchinson, James L.
Hibbert, Nanette
Freeman, Tom C.
Saunders, Philippa T. K.
Norman, Jane E.
author_sort Sharp, Gemma C.
collection PubMed
description An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) <0.05). Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the composition of myometrial tissue at labour. Further work will be necessary to reveal whether these results are solely due to leukocyte infiltration into the myometrium as a mechanism initiating labour, or in addition whether they also represent gene changes in the myocytes themselves. We have made all our data available at www.ebi.ac.uk/arrayexpress/ (accession number E-MTAB-3136) to facilitate progression of this work.
format Online
Article
Text
id pubmed-4866706
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-48667062016-05-18 Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women Sharp, Gemma C. Hutchinson, James L. Hibbert, Nanette Freeman, Tom C. Saunders, Philippa T. K. Norman, Jane E. PLoS One Research Article An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) <0.05). Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the composition of myometrial tissue at labour. Further work will be necessary to reveal whether these results are solely due to leukocyte infiltration into the myometrium as a mechanism initiating labour, or in addition whether they also represent gene changes in the myocytes themselves. We have made all our data available at www.ebi.ac.uk/arrayexpress/ (accession number E-MTAB-3136) to facilitate progression of this work. Public Library of Science 2016-05-13 /pmc/articles/PMC4866706/ /pubmed/27176052 http://dx.doi.org/10.1371/journal.pone.0155413 Text en © 2016 Sharp et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sharp, Gemma C.
Hutchinson, James L.
Hibbert, Nanette
Freeman, Tom C.
Saunders, Philippa T. K.
Norman, Jane E.
Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title_full Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title_fullStr Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title_full_unstemmed Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title_short Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women
title_sort transcription analysis of the myometrium of labouring and non-labouring women
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866706/
https://www.ncbi.nlm.nih.gov/pubmed/27176052
http://dx.doi.org/10.1371/journal.pone.0155413
work_keys_str_mv AT sharpgemmac transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen
AT hutchinsonjamesl transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen
AT hibbertnanette transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen
AT freemantomc transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen
AT saundersphilippatk transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen
AT normanjanee transcriptionanalysisofthemyometriumoflabouringandnonlabouringwomen