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BOR - Papers in Press, published online ahead of print September 26, 2007.
Biol Reprod 2007, 10.1095/biolreprod.107.062182
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biolreprod.107.062182v1
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BIOLOGY OF REPRODUCTION 78, 20–26 (2008)
DOI: 10.1095/biolreprod.107.062182
© 2008 by the Society for the Study of Reproduction, Inc.


Pregnancy; 

Expression of Prothrombin and Protease Activated Receptors in Human Myometrium During Pregnancy and Labor1

Margaret O'Brien 2 3, John J Morrison 3 4, and Terry J Smith 3

National Center for Biomedical and Engineering Science,3 National University of Ireland Galway, Galway, Ireland Department of Obstetrics and Gynecology,4 National University of Ireland Galway, Clinical Science Institute, University College Hospital Galway, Galway, Ireland

ABSTRACT

As thrombin is proposed to be involved in stimulating myometrial contractility during labor and preterm labor, we aimed to investigate the expression of prothrombin (F7), the precursor of thrombin, its receptors, the protease-activated receptor (PAR) family (F2R, F2RL1, F2RL2, and F2RL3), and prothrombinase FGL2 in human myometrium during pregnancy and labor. Messenger RNA and protein were isolated from human pregnant laboring and nonlaboring myometrial tissue and from human primary myometrial smooth muscle cells. Semiquantitative RT-PCR, real-time fluorescence RT-PCR, Western blotting, and fluorescence microscopy were performed to determine the expression levels of F7, FGL2, F2R, F2RL1, F2RL2, and F2RL3 in the myometrial tissues and cells. The expression of mRNA and protein for these molecules is reported for the first time in human myometrium at term pregnancy, at labor, and in the nonpregnant state. Importantly, an increase in F2R and a significant increase in F2RL3 mRNA expression at labor were demonstrated. Statistically significant increases in F2R and F2RL3 protein expression was also detected in human myometrium at labor. Furthermore, FGL2 mRNA expression at labor, and FGL2 protein expression at term pregnancy and at labor was observed in this tissue for the first time. The expression of F7, FGL2, F2R, F2RL1, F2RL2, and F2RL3 in human myometrium reveals that all the machinery necessary for thrombin activation and cellular activity is present in the myometrium during pregnancy and labor. These data, in conjunction with the demonstrated increase in F2R and F2RL3 expression at labor, suggest a principal role for these molecules in the regulation of myometrial function at labor, including preterm labor.

labor, myometrium, parturition, pregnancy, protease activated receptors, prothrombin, uterus


FOOTNOTES

1Supported by the Health Research Board of Ireland and the Higher Education Authority of Ireland's Program for Research in Third Level Institutions.

Correspondence: 2Margaret O'Brien, National Center for Biomedical and Engineering Science, Orbsen Building, National University of Ireland Galway, University Road, Galway, Ireland. FAX: 353 91 492956; e-mail: margaret.obrien{at}nuigalway.ie







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Copyright © 2008 by the Society for the Study of Reproduction.