ENAGenomicsMultiomicsObstetrics and Gynaecology, University of Cambridgehttps://www.ebi.ac.uk/ena/browser/view/PRJNA145997Homo sapiensxref:PubMed:22411014Context: 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. Overall design: 9 paired samples of human myometrium cultured under low (0.6g) or high (2.4g) tensionENAHuman, uterine myometrium, Uterine Muscles, tunica muscularis, human being, Man (Taxonomy), Muscles, Homo sapiens, gravid, uterine smooth muscle, Modern Man, Modern, Uterine., pregnant adult, Muscle, Man, INSDC_feature:misc_RNA, Uterine, Uterine Muscle, human, pregnantHuman, Modern., human being, Man (Taxonomy), Homo sapiens, man, Man, human, Modern ManfalseHomo sapiensEffect of prolonged stretch on transcript profile of human pregnant myometrium2025-09-242014-02-11PRJNA145997GSE31329960622411014