RESEARCH ARTICLE Spontaneous and induced labour are associated with different myometrial proteomes in the human David A. MacIntyre 1 , Roger Smith 1 , George Yeo 2 , Kenneth Kwek 2 , Andrew M. Bisits 1 and Eng-Cheng Chan 1 1 Mothers and Babies Research Centre, Hunter Medical Research Institute, The University of Newcastle, John Hunter Hospital, Newcastle, Australia 2 KK Women’s and Children’s Hospital, Singapore, Singapore Human myometrium undergoes a major phenotypic change at labour likely involving mod- ifications to key regulatory proteins. In some cases, the myometrium fails to activate normally and medical intervention is required to induce labour. In this study, 2-D DIGE was used to examine changes in the myometrial proteome at the time of spontaneous (SL) and induced labour (IL). Proteomic profiles of nonlabouring term myometria (NL, n = 6) were quantitatively compared to SL (n = 6) and prostaglandin/oxytocin-IL term myometria (n = 6). In SL samples, 23 differentially expressed protein spots were detected (9 increased/14 decreased compared to NL, p,0.05). In IL samples, 59 differentially expressed spots were observed (13 increased/46 decreased compared to NL). Comparison of SL and IL proteomes revealed 69 differentially expressed proteins (7 increased/62 decreased). Two proteins consistently decreased in SL and IL samples were identified as transgelin (1.98- and 1.97-fold decrease in SL and IL, respectively) and aB-crystallin (3.27- and 2.49-fold decrease). Levels of desmin and cytosolic phospholipase A2 b were decreased 2.9- and 2.65-fold, respectively only in IL samples. Our results show human labour is accompanied by general downregulation of specific myometrial proteins. Differences exist between SL and IL myometrial proteomes indicating divergence of underlying processes and highlighting the importance of distinguishing these groups in future studies of parturition. Our findings underscore the utility of discovery approaches in investigations of organ-wide pro- tein changes that underlie discrete physiological events including human labour. Received: February 14, 2008 Revised: June 24, 2008 Accepted: July 8, 2008 Keywords: 2-D DIGE / Human myometrium / Labour 288 Proteomics Clin. Appl. 2009, 3, 288–298 1 Introduction At the end of normal human pregnancy, the myometrium undergoes biochemical and structural changes that facilitate transformation from a relaxed, noncontractile phenotype to a highly coordinated and actively contractile phenotype [1, 2]. The mechanisms regulating this process are poorly defined but likely involve changes (e.g. abundance and post-transla- tional) to key regulatory myometrial proteins. While a num- ber of studies describe labour-associated changes in gene expression in the myometrium [3–9], there is a scarcity of information regarding changes in the myometrial proteome at the time of labour. As mRNA levels often correlate poorly with protein concentrations the determination of proteome changes is of importance in understanding the functional changes that occur in the myometrium with the onset of labour. It is unclear whether the changes in the myometrium that occur when labour is artificially induced at term mirror the changes seen when labour occurs spontaneously. How- ever, in those patients who experience successful induction, Correspondence: Dr. Eng-Cheng Chan, Mothers and Babies Re- search Centre, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, 2310 NSW, Australia E-mail: Cheng.Chan@newcastle.edu.au Fax: 161-2-49214394 Abbreviations: cPLA2â, cytosolic phospholipase A2 b; Cy, cya- nine; IL, induced labour; NL, no labour; SL, spontaneous labour DOI 10.1002/prca.200800050  2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.clinical.proteomics-journal.com