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Lookup NU author(s): Professor Steve RobsonORCiD,
Emeritus Professor Nick Europe-Finner
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Objective: This study was undertaken to investigate the effects of 3 histone deacetylase inhibitors on human uterine contractility. Study Design: Biopsy specimens of human myometrium were obtained at elective cesarean section (n = 18). Dissected myometrial strips suspended under isometric conditions, undergoing spontaneous, and oxytocin-induced contractions, were subjected to cumulative additions of 3 histone deacetylase inhibitors: trichostatin A, suberic bishydroxamate (1 nmol/L-10 μmol/L) and valproic acid (100 nmol/L - 1 mmol/L). Control experiments were run simultaneously. Integrals of contractile activity were measured by using the PowerLab hardware unit and Chart v3.6 software. Data were analyzed by using 1-way analysis of variance, followed by post hoc analysis. Results: All 3 histone deacetylase inhibitor compounds exerted a potent and cumulative inhibitory effect on spontaneous (n = 18) and oxytocin-induced (n =18) contractility. The mean maximal inhibition values for the 3 compounds were as follows: trichostatin A, 46-54% (P < .05); valproic acid, 35-36% (P < .05); and suberic bishydroxamate, 53-65% (P < .05). Conclusion: The histone deacetylase inhibitors trichostatin A, valproic acid, and suberic bishydroxamate exerted a potent inhibitory effect on human uterine contractions. This raises the possibility that this new class of compounds may have tocolytic potential, in addition to their current clinical indications. We speculate that this inhibitory effect may be linked, at least in part, to the ability of histone deacetylase inhibitors to induce the expression of genes involved in maintaining myometrial quiescence via epigenetic mechanisms but may also potentially involve nonepigenetic pathways. © 2008 Mosby, Inc. All rights reserved.
Author(s): Moynihan AT, Hehir MP, Sharkey AM, Robson SC, Europe-Finner GN, Morrison JJ
Publication type: Article
Publication status: Published
Journal: American Journal of Obstetrics and Gynecology
Pages: 167 E1-E7
ISSN (print): 0002-9378
ISSN (electronic): 1097-6868
Publisher: Mosby, Inc.
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