Identifying Genetic Networks Underlying Myometrial Transition to Labor

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2005 Feb 8

PMID 15693941

Citations 34

Authors

Nathan Salomonis

Nathalie Cotte

Alexander C Zambon

Katherine S Pollard

Karen Vranizan

Scott W Doniger

Gregory Dolganov

Bruce R Conklin

Affiliations

Soon will be listed here.

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 transcriptional 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.

Citing Articles

Multiple pregnancies, the myometrium and the role of mechanical factors in the timing of labour.

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β3 adrenergic receptor activation modulates connexin 43 activity to relax human myometrium.

Asif H, Barnett S, Saxon D, Younis H, Buxton I Cell Signal. 2023; 106:110640.

PMID: 36841274 PMC: 10134909. DOI: 10.1016/j.cellsig.2023.110640.

MYB and ELF3 differentially modulate labor-inducing gene expression in myometrial cells.

Shchuka V, Khader N, Dorogin A, Shynlova O, Mitchell J PLoS One. 2023; 18(1):e0271081.

PMID: 36595497 PMC: 9810189. DOI: 10.1371/journal.pone.0271081.

Transposable Elements Continuously Remodel the Regulatory Landscape, Transcriptome, and Function of Decidual Stromal Cells.

Mika K, Lynch V Genome Biol Evol. 2022; 14(12).

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Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation.

Wendremaire M, Lopez T, Barrichon M, Zhang H, Hadi T, Ye X Cells. 2022; 11(6).

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