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Status |
Public on Jun 08, 2011 |
Title |
Effect of Medroxyprogesterone Acetate on Transcript Profile of Human Pregnant Myometrium |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression.
Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen.
Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR.
Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001).
Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition.
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Overall design |
9 paired samples of human myometrium treated with MPA (10-7M) or vehicle
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Contributor(s) |
Cordeaux Y, Tattersall M, Charnock-Jones DD, Smith GC |
Citation(s) |
20843944 |
Submission date |
Jul 15, 2010 |
Last update date |
Mar 20, 2017 |
Contact name |
D. Stephen Charnock-Jones |
E-mail(s) |
dscj1@cam.ac.uk
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Organization name |
University of Cambridge
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Department |
Obstetrics and Gynaecology
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Street address |
The Rosie Hospital
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City |
Cambridge |
ZIP/Postal code |
CB2 0SW |
Country |
United Kingdom |
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Platforms (1) |
GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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Samples (18)
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Relations |
BioProject |
PRJNA127847 |
Supplementary file |
Size |
Download |
File type/resource |
GSE22961_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR |
Processed data included within Sample table |
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