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| Status |
Public on Jun 15, 2012 |
| Title |
Effect of prolonged stretch on transcript profile of human pregnant myometrium |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Context: Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. Objectives: To identify a targetable mechanism mediating the effect of stretch on human myometrium. Design: Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Results: Increased stretch for 24 or 65 h increased potassium-induced and oxytocin-induced contractility. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP by stretch was confirmed in a separate series of 10 samples using qRT-PCR (2.8-fold, P = 0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 3 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h respectively) significantly reduced potassium chloride and oxytocin-induced contractility. Conclusion: Stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium in GRP receptor antagonists ameliorates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy.
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| Overall design |
9 paired samples of human myometrium cultured under low (0.6g) or high (2.4g) tension
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| Contributor(s) |
Tattersall M, Cordeaux Y, Charnock-Jones DS, Smith GC |
| Citation(s) |
22411014 |
| Submission date |
Aug 10, 2011 |
| Last update date |
Mar 20, 2017 |
| Contact name |
D. Stephen Charnock-Jones |
| E-mail(s) |
dscj1@cam.ac.uk
|
| Organization name |
University of Cambridge
|
| Department |
Obstetrics and Gynaecology
|
| Street address |
The Rosie Hospital
|
| 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 |
PRJNA145997 |
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