Morphologic and histochemical evidence for the occurrence of collagenolysis and for the role of neutrophilic polymorphonuclear leukocytes during cervical dilation

Junqueira, L. C.; Zugaib, Marcelo; Montes, G. S.; Toledo, O. M. S.; Krisztán, R. M.; Shigihara, Kae

doi:10.1016/0002-9378(80)90248-3

Cited by 355 publications

(163 citation statements)

References 14 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…However, their morphology was very typical for each hormone applied: edema development under E2 treatment, reduced density and organization of collagen fibers for RLX application and for the combined application of RLXCE2 a massive eosinophil cell invasion, as well as a moderate focal edema development with reduced density and organization of collagen fibers. Cervical ripening is dependent on the disruption of ordered collagen bundles (Sherwood et al 1993) and polymorphonuclear leukocyte invasion in the cervix of humans (Junqueira et al 1980). In our experiments, the combined application of RLX and E2 resulted exactly within these actions.…”

Section: Discussionsupporting

confidence: 59%

The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

Simon¹,

Einspanier

2009

Reproduction

View full text Add to dashboard Cite

Controversy still exists regarding the involvement of relaxin (RLX) in cervical reorganization throughout parturition in the human, despite its well-known role in facilitating extensive extracellular matrix (ECM) remodeling in diverse organs. Therefore, the aim of the present study was to examine the influence of RLX and estrogen (E2) on the cervical tissue of the common marmoset monkey. Two experimental designs were used: 1) in vivo analysis of the intracervical diameter under locally applied RLX and 2) ovariectomized (ov) marmosets were treated systemically with either recombinant human (rh) RLX, E2 or rhRLXCE2 to examine their action on the cervix. In vivo-locally applied rhRLX induced a distinct and significant widening of the cervix (before: 4.8G1.1 mm versus after: 5.7G0.9 mm in diameter; P!0.030, MVGS.E.M.). This widening effect was most pronounced in animals without previous pregnancies. In vitro investigation of cervical tissue showed significantly increased wet weights after all three hormone treatments (E2: 0.27G0.07 g, RLX: 0.25G0.04 g, E2C RLX: 0.30G0.11 g; all P!0.05; MVGS.E.M.) versus controls (0.10G0.04 g). Furthermore, morphological changes such as loosening of the connective tissue structure and decline in collagen content, an increase in the number of eosinophils, increased the expression of matrix metalloproteinases (MMP1) and MMP2, as well as gene and protein expression of the RLX receptor RXFP1 could be detected in the cervical tissue after all hormone treatments, compared with controls. In summary, RLX has a potent widening effect on the cervix of the common marmoset monkey. Although E2 is not required for this RLX effect, a combined application of E2 and RLX induced the most prominent cervical ripening.

show abstract

Section: Discussionsupporting

confidence: 59%

The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

Simon¹,

Einspanier

2009

Reproduction

View full text Add to dashboard Cite

show abstract

“…Moreover, the expression of these genes was markedly up-regulated in response to TNF-␣ and IL-1␤, cytokines that may participate in the normal process of cervical ripening or the premature remodeling of the cervix associated with preterm labor. 4,5 We also obtained preliminary evidence for CSMC expression of MMP-13, an enzyme that degrades fibrillar collagens and also activates MMP-9 (unpublished observations). The abundance of MMP-13 mRNA was much lower than that of MMP-1, -3, and -9 mRNAs but, like these other MMP transcripts, MMP-13 message levels in the CSMC were increased by cytokine treatment.…”

Section: Discussionmentioning

confidence: 68%

“…3 The profound remodeling of the cervical extracellular matrix occurs coincidentally with a dramatic influx of white blood cells. 4,5 Thus, the process of cervical ripening has been likened to an inflammatory response.…”

mentioning

confidence: 99%

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

Watari

DiSanto

et al. 1999

The American Journal of Pathology

165

View full text Add to dashboard Cite

The process of cervical ripening has been likened to an inflammatory reaction associated with the catabolism of cervical extracellular matrix by enzymes released from infiltrating leukocytes. We hypothesized that smooth muscle cells in the cervix also participate in this process and that pro-inflammatory cytokines act on cervical smooth muscle cells (CSMC) to provoke the expression of matrix-degrading enzymes. We treated primary cultures of human CSMC with tumor necrosis factor-␣ (TNF-␣) and examined expression of the elastinolytic enzyme , cathepsin S, the collagen metabolizing matrix metalloproteinases (MMP)-1 , -3 , -9 , and the tissue inhibitor of metalloproteinase (TIMP)-1 and -2. A time course analysis revealed that 10 ng/ml of TNF-␣ induced cathepsin S, MMP-1 , -3 , and -9 mRNA expression with the maximal response observed after 24 -48 hours. TNF-␣ induced cathepsin S , MMP-1 , -3 , and -9 mRNA expression in a dose-dependent manner: the maximal effect was observed at a concentration of 10 ng/ml , with appreciable increases observed at concentrations of 0.1 to 1.0 ng/ml. In contrast , TIMP-1 and -2 mRNAs were not significantly increased by TNF-␣ treatment. Interleukin-1␤ produced a pattern of gene expression in the CSMC similar to that observed following TNF-␣ treatment. Western blot analysis and zymography confirmed the induction of proMMP-1 , -3 , and -9 in response to TNF-␣, but MMP-2 immunoreactivity and zymographic activity were unaffected. TNF-␣ increased secretion of procathepsin S , but did not affect TIMP-1 and reduced TIMP-2 production. We conclude that CSMC are targets of pro-inflammatory cytokines, which induce a repertoire of enzymes capable of degrading the cervical extracellular matrix. The induction of these enzymes may facilitate the normal ripening of the cervix at term and participate in the The human cervix is composed primarily of connective tissue consisting mainly of fibrillar collagens, elastin, and glycosaminoglycans.

show abstract

“…Immune cells that infiltrate the cervix during cervical ripening have long been considered to play a key role in ECM degradation and remodeling via activation of proinflammatory signals and the release of MMPs that breakdown collagen (Liggins 1981). Numerous studies based on immunohistochemical analysis of immune cells suggest a functional role of macrophages or neutrophils in the process of cervical ripening (Junqueira et al 1980, Luque et al 1998, Mackler et al 1999, Young et al 2002, Osman et al 2003. The fact that antibodies used for assessment of macrophages and neutrophils can also recognize monocytes and other myeloid cells and the recent appreciation that a single type of immune cell (e.g.…”

Section: Cervical Ripening and Dilation: Accelerated Phases Of Remodementioning

confidence: 99%

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

Mahendroo¹

2012

Reproduction

177

148

View full text Add to dashboard Cite

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.

show abstract

Morphologic and histochemical evidence for the occurrence of collagenolysis and for the role of neutrophilic polymorphonuclear leukocytes during cervical dilation

Cited by 355 publications

References 14 publications

The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus)

Pro-Inflammatory Cytokines Induce Expression of Matrix-Metabolizing Enzymes in Human Cervical Smooth Muscle Cells

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

Contact Info

Product

Resources

About