The transcriptome of the uterine cervix before and after spontaneous term parturition

Hassan, Sonia S.; Romero, Roberto; Haddad, Ramsi; Hendler, Israel; Khalek, Nahla; Tromp, Gerard; Diamond, Michael P.; Sorokin, Yoram; Malone, John M.

doi:10.1016/j.ajog.2006.06.021

Cited by 118 publications

(95 citation statements)

References 17 publications

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“…Many other genes not previously known to be differentially regulated with cervical ripening were also identified. (6) In contrast to cervical dilation after term labor, [12,15] inflammation-related genes did not emerge as differentially expressed with cervical ripening.…”

Section: Commentmentioning

confidence: 99%

“…This procedure has been used extensively by investigators in the United States, Europe and other continents [2,3,6,7,[9][10][11]13,15,16,18,23,[25][26][27][28]31,35,[37][38][39][40]. Half centimeter biopsies were obtained transvaginally from the anterior lip of the cervix at the 12 o'clock position and immediately snap frozen in liquid nitrogen or placed in RNAlater 1 (Ambion, Inc., Austin, TX) and stored at -708C.…”

Section: Methodsmentioning

confidence: 99%

“…The study of the transcriptome (changes in gene transcription) in a particular tissue provides a comprehensive, systematic and unbiased description of genes differentially expressed in a specific condition or point in time [15]. The aim of this study was to characterize the cervical transcriptome in patients with a ripe cervix at term before the onset of labor compared to those with an unripe cervix.…”

Section: Introductionmentioning

confidence: 99%

“…The use of high-dimensional biology techniques allows for the examination of the genome, transcriptome [15] proteome, and metabolome. The study of the transcriptome (changes in gene transcription) in a particular tissue provides a comprehensive, systematic and unbiased description of genes differentially expressed in a specific condition or point in time [15].…”

Section: Introductionmentioning

confidence: 99%

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The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

Hassan¹,

Romero²,

Tarca³

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective. The aim of this study was to identify changes in the cervical transcriptome in the human uterine cervix as a function of ripening before the onset of labor. Study Design. Human cervical tissue was obtained from women at term not in labor with ripe (n ¼ 11) and unripe (n ¼ 11) cervices and profiled using Affymetrix GeneChip 1 HGU133Plus2.0 arrays. Gene expression was analyzed using a moderated t-test (False Discovery Rate 5%). Gene ontology and pathway analysis were performed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for confirmation of selected differentially expressed genes. Results.(1) Ninety-one genes were differentially expressed between ripe and unripe groups. (2) Cervical ripening was associated with enrichment of specific biological processes (e.g. cell adhesion, regulation of anatomical structure), pathways and 11 molecular functions (e.g. extracelluar matrix (ECM)-structural constituent, protein binding, glycosaminoglycan binding). (3) qRT-PCR confirmed that 9 of 11 tested differentially expressed genes (determined by microarray) were upregulated in a ripe cervix (e.g. MYOCD, VCAN, THBS1, COL5A1). (4) Twenty-three additional genes related to ECM metabolism and adhesion molecules were differentially regulated (by qRT-PCR) in ripe cervices. Conclusion.(1) This is the first description of the changes in the human cervical transcriptome with ripening before the onset of labor. (2) Biological processes, pathways and molecular functions were identified with the use of this unbiased approach. (3) In contrast to cervical dilation after term labor, inflammation-related genes did not emerge as differentially regulated with cervical ripening. (4) Myocardin was identified as a novel gene upregulated in human cervical ripening.

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Section: Commentmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

Hassan¹,

Romero²,

Tarca³

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

Self Cite

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“…M1 and M2 macrophages), further muddies interpretation of immunohistochemical studies on human and animal models. The limited studies that utilize wellcharacterized tissues collected during ripening before birth suggest no increase in the proinflammatory chemoattractant, Il8, while microarray studies that compare gene expression patterns at term before ripening to postpartum reveal increased expression of proinflammatory genes after vaginal delivery but not during cervical ripening (Sakamoto et al 2004, Hassan et al 2006. Studies on mice in which precisely timed cervical tissue can be obtained before, during, and after term cervical ripening, the use of more sophisticated technologies to allow identification of myeloid cells via multiple surface markers and identification of markers that distinguish macrophages of varying phenotypes have been instrumental in clarifying the contribution of immune cells to both physiological and pathophysiological remodeling and emphasize the need to reevaluate more critically the role of immune cells in human term cervical ripening.…”

Section: Relevance To Cervical Remodeling In Womenmentioning

confidence: 99%

Cervical remodeling in term and preterm birth: insights from an animal model

Mahendroo¹

2012

Reproduction

177

148

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Proper cervical function is essential for a normal pregnancy and birth to occur. Understanding the mechanisms that take place in normal pregnancy will allow a better comprehension of the complications involved in premature cervical remodeling and lead to better methods of diagnostics and prevention for preterm birth. Unfortunately, human samples are not easily available, and samples that are collected are often confounded by variations in timing and region of cervix from which sample is collected. Animal models, specifically the mouse, have facilitated a great deal of exploration into the mechanisms of cervical function and pathways of preterm birth. This review highlights some of the groundbreaking discoveries that have arisen from murine research including 1) the identification of early pregnancy changes in collagen fibril processing and assembly that result in progressive modifications to collagen architecture with subsequent loss of tissue stiffness during pregnancy, 2) the determination that immune cells are not key to cervical ripening at term but have diverse phenotypes and functions in postpartum repair, and 3) the finding that the process of preterm cervical ripening can differ from term ripening and is dependent on the etiology of prematurity. These findings, which are relevant to human cervical biology, provide new insights that will allow targeted studies on the human cervix as well as identify potential biomarkers for early detection of premature cervical ripening and development of improved therapies to prevent premature ripening of the cervix and subsequent preterm birth.

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Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes

Rosa¹,

Tarsitano²,

Hyslop³

et al. 2007

Microscopy Res & Technique

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In some animals, such as mice and guinea pigs, a hormonally controlled mechanism increases the flexibility of the pubic symphysis and enhances the cervical remodeling necessary for safe delivery. Cervical ripening during pregnancy is associated with a paradoxical influx of leukocytes. However, the changes in cell metabolism during relaxation of the mouse pubic symphysis for delivery have not been extensively studied. In this work, we used light microscopy and transmission and scanning electron microcopy, as well as immunohistochemistry and Western blotting for MMP-8, to investigate the involvement of granulocytes or resident stromal cells in the relaxation of the virgin pubic symphysis during late pregnancy (days 18 and 19, before delivery) in vivo and in explanted joints. MMP-8 was studied because this collagenase is a hallmark for cervical ripening associated with the influx of granulocytes during late pregnancy. Extensive dissolution and disorganization of the extracellular matrix was seen around fibroblastic-like cells in late pregnancy. In contrast to the cervix (positive control), morphological and immunohistochemical analyses revealed that there was no characteristic cellular inflammatory response in the interpubic tissue. Staining for MMP-8 was observed in chondroid and fibroblastic-like cells of virgin and relaxed interpubic ligament, respectively. However, no granulocytes were seen during the extensive remodeling of the pubic joint in late pregnancy. These results indicate that constitutive stromal cells may have an important role in tissue relaxation during remodeling of the pubic symphysis in pregnancy.

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The transcriptome of the uterine cervix before and after spontaneous term parturition

Cited by 118 publications

References 17 publications

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: Identification of novel molecular functions involved in this process

Cervical remodeling in term and preterm birth: insights from an animal model

Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes

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