Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition

The mechanisms that lead to the onset of human parturition are still unknown, although selected critical factors have been identified. To investigate the changes in myometrial gene expression associated with parturition, we used two macroarrays each containing 1176 different complementary human cDNA clones. Methods involving hierarchical clustering and conventional statistical analysis allowed us to generate a profile of genes expression at three stages of late pregnancy: preterm (29 wk amenorrhea); full term, not in labor (38 wk amenorrhea); and full term in labor (39 wk amenorrhea). Only 4% of the genes investigated were differentially expressed between the preterm and term groups (P < 0.05). These genes could be clustered as groups of either down-regulated or up-regulated transcripts. The changes in transcript abundance were particularly marked between the preterm and term stages of gestation, whereas the differences between term not in labor and term in labor were less pronounced. The parturition was characterized by a massive down-regulation of a large panel of developmental, cell adhesion molecule and proliferation-related genes, along with the up-regulation of inflammatory, contraction and apoptosis associated genes. We propose that the mechanisms of parturition consist primarily in the arrest of the processes of myometrial development, a step that might be essential to allow the uterus to recover appropriate contractile function before delivery.

Section: Inflammation-associated Genesmentioning

confidence: 70%

“…2 Correspondence. FAX: 33 play a role in the onset of labor. The silencing of the myometrial contractile function is conditioned by a predominant functional cAMP/cGMP system, whereas contractions are under the control of agonist-induced calcium mobilization via the phospholipase C pathway.…”

Section: Introductionmentioning

confidence: 99%

A Functional Genomic Study to Identify Differential Gene Expression in the Preterm and Term Human Myometrium1

Charpigny

Leroy

Breuiller-Fouché

et al. 2003

“…Despite these differences in technique and method of uterine sampling, comparisons of gene expression profiles of human myometrium before and after the onset of labor agree that, compared with studies conducted in murine and rat pregnancy, changes in gene expression at the transcriptional level in myometrial tissues obtained from laboring women are minimal, and the predominant changes were associated with the inflammatory response. Findings are concordant for at least five genes, all of which are involved in the inflammatory response; namely, homolog of murine myxovirus resistance 1 (MX1), interferon alpha-inducible protein (G1P3), interferon-induced transmembrane protein 1 (IFITM1; [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]), FcgammaRIIIA/CD16 (FCGR3A), and alpha-1-antichymotrypsin (SERPINA3).…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence, however, that several genes are coordinately regulated in myometrial tissues before or during parturition [5][6][7]. In comparing myometrial tissue samples from laboring and nonlaboring women, differential gene expression has been identified in estrogen and progesterone receptors [8], intercellular adhesion molecule-1 [9], interleukin-8 [10], 15-hydroxyprostaglandin dehydrogenase [11], cyclooxygenase-1 and -2 (COX-1 and COX-2; also known as prostaglandinendoperoxide synthase 1 and 2, PTGS1 and PTGS2) [12], and the myometrial gap junction protein connexin-43 [13]. This list is by no means exhaustive, and many of the molecular changes resulting in myometrial tissue remodeling and myometrial contractions are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

Human Myometrial Gene Expression Before and During Parturition1

Havelock

Keller

Muleba

et al. 2005

143

103

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.

“…As term approaches, remodeling of the cervix is characterized by reduced density of cell nuclei, degradation of extracellular matrix collagen content and structure, and immigration of immune cells [17][18][19][20]. By the day before birth, immune cells have immigrated into the stroma and perimetrium of the cervix in mice [21,22] and rats [23,24].…”

Section: Introductionmentioning

confidence: 99%

Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform

Yellon

Oshiro

Chhaya

et al. 2011

Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition.