Human Myometrial Gene Expression Before and During Parturition1

Abstract

Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding of the coordinated regulation of myometrial contractions during parturition. The objective of this study was to compare the gene expression profiles of human fundal myometrium from pregnant women before and after the onset of labor using a functional genomics approach, and to further characterize the spatial and temporal expression patterns of three genes believed to be important in parturition. Fundal myometrial mRNA was isolated from five women in labor and five women not in labor, and analyzed using human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain reaction using myometrial RNA from pregnant women in labor or not in labor was used to examine mRNA levels for three of the genes; namely, prostaglandin-endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor (OXTR). The spatial expression pattern of these genes throughout the pregnant uterus before and after labor was also determined. Immunolocalization of cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and myometrium were analyzed by immunohistochemistry. Few genes were differentially expressed in fundal myometrial tissues at term with the onset of labor. However, there appears to be a subset of genes important in the parturition cascade. The cellular properties of S100A9, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor.

Advances in the role of oxytocin receptors in human parturition

“…This is associated with an upregulation of OTR mRNA levels and a strong increase in the density of myometrial OTRs reaching a peak during early labour [30]. This was first described in rats [13], and subsequently demonstrated in rabbits and humans [12,31].…”

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

“…Calgranulin B is the major calcium-binding protein of neutrophils and monocytes (Vogl et al 2004), and stimulates proliferation of fibroblasts, suggesting that it plays a role in chronic inflammation (Shibata et al 2004). The cellular properties of calgranulin B, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor (Havelock et al 2005). In contrast to that, studies of MRP-14(K/K) mice showed that they have no obvious phenotype and are fertile (Hobbs et al 2003).…”

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.…”

“…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.…”