A molecular signature of an arrest of descent in human parturition

Abstract

Objective-This study was undertaken to identify the molecular basis of an arrest of descent.Study Design-Human myometrium was obtained from women in term labor (TL; n=29) and arrest of descent (AODes, n=21). Gene expression was characterized using Illumina® HumanHT-12 microarrays. A moderated t-test and false discovery rate adjustment were applied for analysis. Confirmatory qRT-PCR and immunoblot was performed in an independent sample set.Results-400 genes were differentially expressed between women with an AODes compared to those with TL. Gene Ontology analysis indicated enrichment of biological processes and molecular functions related to inflammation and muscle function. Impacted pathways included inflammation and the actin cytoskeleton. Overexpression of HIF1A, IL-6, and PTGS2 in AODES was confirmed. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-We have identified a stereotypic pattern of gene expression in the myometrium of women with an arrest of descent. This represents the first study examining the molecular basis of an arrest of descent using a genome-wide approach.

Neuromedin B and Its Receptor Influence the Activity of Myometrial Primary Cells In Vitro Through Regulation of Il6 Expression via the Rela/p65 Pathway in Mice1

“…Moreover, native and transfected rat Nmbr exhibit similar binding and signaling characteristics in BALB/3T3 cells [13,]. These results have clearly demonstrated that Nmbr is involved in parturition via a number of signaling pathways in addition to its function in the regulation of the nervous system [33][34][35][36][37].…”

Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses

“…Transient decreases of oxygenation, pH, and ATP, all of which if sustained can decrease contractile activity, occur in vivo with each contraction (3)(4)(5). Hypoxia regulates a large number of genes, including those governing metabolism and function in many tissues, and changes in genes associated with hypoxia have been identified as key findings in transcriptomic studies of poorly laboring women (6,7). Chaemsaithong et al and Mittal et al confirmed changes in hypoxia-inducible factor 1a (HIF1a) using RT-PCR, as well as overexpression of cyclooxygenase-2 (COX2) in myometrium and endothelial NOS, which is important for blood vessel dilation.…”

Characterization of the myometrial transcriptome in women with an arrest of dilatation during labor

“…In human pregnancy, HIF1A plays a role in the survival of hematopoietic precursors, embryonic vasculature [146] and trophoblast differentiation [3,44,119] during development [2]. Mittal et al [123] demonstrated a higher expression of HIF1A in the myometrium of patients with an arrest of descent (AOD) than in those with spontaneous term labor. Our findings suggest that during the course of failure to progress in labor (AODIL or AOD), a change in the expression of factors responsible for sensing tissue hypoxia occurs.…”

“…These findings are consistent with prior reports from our group that focus on arrest of descent. [123]. Mittal et al [123] first characterized the myometrial transcriptome of patients with an arrest of descent; 400 genes were differentially expressed.…”

“…Recently, the transcriptome of the myometrium in patients with an “arrest of descent” [123] and “labor dystocia” have been reported [23]. However, the transcriptome of human myometrium in AODIL has not yet been investigated.…”