Microarray Analysis of Uterine Gene Expression in Mouse and Human Pregnancy

Abstract

Improved care of infants born prematurely has increased their survival. However, the incidence of preterm labor has not changed. To understand the processes involved in preterm labor, we used oligonucleotide microarrays to study gene expression in murine and human uterus during pregnancy. The induction of enzymes for prostaglandin synthesis was used as a marker for important changes during pregnancy because prostaglandins strongly contribute to both human and murine labor. We identified 504 genes that changed at least 2-fold between d 13.5 and 19.0 in the gravid mouse uterus. In the pregnant human myometrium, we found 478 genes that changed at least 2-fold in either term or preterm labor compared with preterm nonlabor specimens and 77 genes that significantly varied in both preterm and term labor. Patterns of gene regulation within functional groups comparing human preterm and term labor were similar, although the magnitude of change often varied. Surprisingly, few genes that changed significantly throughout pregnancy were the same in the mouse and human. These data suggest that functional progesterone withdrawal in human myometrium may not be the primary mechanism for labor induction, may implicate similar mechanisms for idiopathic preterm and term labor in humans, and may identify novel targets for further study.

Gene and protein expression in the myometrium in pregnancy and labor

“…Functional genomics has arrived at the study of parturition in different species: mice (Bethin et al 2003, Salomonis et al 2005; rats (Girotti & Zingg 2003) and humans (Chan et al 2002, Marvin et al 2002a, 2002b, Tashima et al 2002, Bethin et al 2003, Charpigny et al 2003, Keelan et al 2003, Esplin et al 2005, Havelock et al 2005. Also in different tissues: myometrium (Aguan et al 2000, Chan et al 2002, Bethin et al 2003, Charpigny et al 2003, Esplin et al 2005, Havelock et al 2005, Salomonis et al 2005; primary cultures of human myometrial cells ; fetal membranes (Muhle et al 2001, Chen et al 2002, Marvin et al 2002a, 2002b, Tashima et al 2002, Keelan et al 2003 and trophoblasts (Chen et al 2002, Kato et al 2002.…”

“…Also in different tissues: myometrium (Aguan et al 2000, Chan et al 2002, Bethin et al 2003, Charpigny et al 2003, Esplin et al 2005, Havelock et al 2005, Salomonis et al 2005; primary cultures of human myometrial cells ; fetal membranes (Muhle et al 2001, Chen et al 2002, Marvin et al 2002a, 2002b, Tashima et al 2002, Keelan et al 2003 and trophoblasts (Chen et al 2002, Kato et al 2002. Various methodologies have been used: suppression subtractive hybridization (SSH) (Chan et al 2002) or microarrays for most of the previous cited studies.…”

“…All investigators have reported genes differentially regulated during parturition and multiple novel candidate markers for preterm labor (Wu et al 1999, Chan et al 2002, Marvin et al 2002a, 2002b. They contributed to shed light on specific pathophysiological issues such as the patterns of expression of cytokines in the fetal membranes and decidua particularly in the presence of intrauterine infection (Keelan et al 2003) or on the induction of enzymes for prostaglandin synthesis (Bethin et al 2003) which are commonly associated with the onset of labor. Groups of genes with as yet unknown functional connection to these pathologies were also found coordinately expressed.…”

“…It gives an overall picture of the changes that the uterine muscle undergoes in its adaptation to gestation. Two studies have described the changes in gene expression in the myometrium in preterm patients not in labor (PTNIL) versus patients at TNIL (Bethin et al 2003, Charpigny et al 2003 and two additional studies have described the changes in gene expression in the myometrium in patients at TNIL versus patients at term in labor (TIL) (Esplin et al 2005, Havelock et al 2005. Other studies could not be compiled directly, either because they did not provide sufficient information on the genes being studied (i.e.…”

“…KEGG is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information (http://www.genome.jp/kegg/pathway.html). Because relevant raw data for myometrium microarrays were not always available, input data files for use with the Onto-Tools software modules were built on gene lists reported in published papers or, when available, on the complete gene expression data set, deposited as supplemental data at a public Internet site, see Bethin et al 2003, Charpigny et al 2003, Rehman et al 2003. Drawbacks and limitations inherent to the use of Onto-Tools or of their cognate alternatives for ontological analysis, have been reviewed .…”