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Open Access Research

Identifying genetic networks underlying myometrial transition to labor

Nathan Salomonis12, Nathalie Cotte13, Alexander C Zambon13, Katherine S Pollard4, Karen Vranizan15, Scott W Doniger1, Gregory Dolganov3 and Bruce R Conklin1236*

Author Affiliations

1 Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA

2 Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, 513 Parnassus Avenue, San Francisco, CA 94143, USA

3 Department of Medicine, Cardiovascular Research Institute, University of California, 505 Parnassus Avenue, San Francisco, CA 94143, USA

4 Center for Biomolecular Science and Engineering, University of California, 1156 High Street, Santa Cruz, CA 95064, USA

5 Functional Genomics Laboratory, University of California, Berkeley, CA 94720-3860, USA

6 Cellular and Molecular Pharmacology, University of California, 600 16th Street, San Francisco, CA 94143-2140, USA

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Genome Biology 2005, 6:R12  doi:10.1186/gb-2005-6-2-r12

Published: 28 January 2005

Abstract

Background

Early transition to labor remains a major cause of infant mortality, yet the causes are largely unknown. Although several marker genes have been identified, little is known about the underlying global gene expression patterns and pathways that orchestrate these striking changes.

Results

We performed a detailed time-course study of over 9,000 genes in mouse myometrium at defined physiological states: non-pregnant, mid-gestation, late gestation, and postpartum. This dataset allowed us to identify distinct patterns of gene expression that correspond to phases of myometrial 'quiescence', 'term activation', and 'postpartum involution'. Using recently developed functional mapping tools (HOPACH (hierarchical ordered partitioning and collapsing hybrid) and GenMAPP 2.0), we have identified new potential transcriptional regulatory gene networks mediating the transition from quiescence to term activation.

Conclusions

These results implicate the myometrium as an essential regulator of endocrine hormone (cortisol and progesterone synthesis) and signaling pathways (cyclic AMP and cyclic GMP stimulation) that direct quiescence via the transcripitional upregulation of both novel and previously associated regulators. With term activation, we observe the upregulation of cytoskeletal remodeling mediators (intermediate filaments), cell junctions, transcriptional regulators, and the coordinate downregulation of negative control checkpoints of smooth muscle contractile signaling. This analysis provides new evidence of multiple parallel mechanisms of uterine contractile regulation and presents new putative targets for regulating myometrial transformation and contraction.