Matrix metalloproteinase‐8 correlates with the cervical ripening process in humans

Sennström, Maria; Brauner, Annelie; Byström, Birgitta; Malmström, Anders; Ekman, Gunvor

doi:10.1034/j.1600-0412.2003.00249.x

Cited by 45 publications

(50 citation statements)

References 38 publications

(47 reference statements)

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“…The dramatic ripening of the cervix involves a cascade of MMPs that includes MMP-8 (collagenase-2), MMP-3 (stromelysin), and gelatinases (MMP-2 and -9). Indeed, high levels of MMP-8 (Sennström et al, 2003) and MMP-2 and -9 (Stygar et al, 2002) have been observed in the stromal tissue of ripened cervix in women at parturition, and MMP-3 has been detected in rat cervix, also at parturition (Chien et al, 2005).…”

Section: Discussionmentioning

confidence: 96%

“…The influx of inflammatory cells coincides with a rise in the levels of matrix metalloproteinases (MMP) -1, -13, and -8 that degrade fibrillar collagen, and MMP-9 that degrades basement membranes (Aronsson et al, 2005;Rath et al, 1998;Sennström et al, 2003). MMP-8, also known as neutrophil collagenase-2, preferentially cleaves type I collagen (Balbín et al, 1998;Libert, 2006;Maymon et al, 2000;Sennström et al, 2003;Van Lint and Sulkala et al, 2007).…”

Section: Introductionmentioning

confidence: 96%

“…MMP-8, also known as neutrophil collagenase-2, preferentially cleaves type I collagen (Balbín et al, 1998;Libert, 2006;Maymon et al, 2000;Sennström et al, 2003;Van Lint and Sulkala et al, 2007). MMP-8 is normally stored in neutrophil granules as pro-MMP-8 and is secreted during acute inflammatory processes (Nagase et al, 1991).…”

Section: Introductionmentioning

confidence: 96%

“…MMP-8 is normally stored in neutrophil granules as pro-MMP-8 and is secreted during acute inflammatory processes (Nagase et al, 1991). Sennström et al (2003) reported an 80-fold increase in MMP-8 levels during cervical ripening and suggested that this MMP may be important for initiating remodeling in female reproductive tissue.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Nitric oxide (NO) may be involved in the process of cervical ripening and may cause the inflammatory-like changes inducing arterial dilation, leakage of fluid to the extracellular matrix, and leukocyte infiltration [15]. Nitric oxide may also regulate the activity of the metalloproteinases and induce prostaglandin production by stimulating cyclooxygenase activity [16].…”

Section: Discussionmentioning

confidence: 99%

Frequency domain near‐infrared spectroscopy of the uterine cervix during cervical ripening

Baños

Wolf²,

Grawe

et al. 2007

Lasers Surg Med

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Objective: Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor has a substantial inter-and intraobserver variability. We used frequency domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during druginduced cervical ripening. Methods: Ten volunteers scheduled for abortion were examined. Optical properties of the uterine cervix were measured and physiological parameters were calculated prior to and after induction of cervical ripening using topical misoprostol. Mean relative changes, standard error of the mean as well as statistical significance using the t-test were calculated for oxy-and deoxyhemoglobin, total hemoglobin, oxygen-saturation, and water. The wavelength-dependent decrease of scattering (scatter power) was calculated by an exponential fit and tested with the Wilcoxon test. Results: Misoprostol induced a decrease in total hemoglobin of 21+/-6% (P<0.05), a decrease in oxyhemoglobin of 22+/-6% (P<0.05), a decrease in deoxyhemoglobin of 16+/-11% and an increase of 368% (P<0.005) in water content. The scatter power was significantly lower (P<0.05) after cervical ripening. Conclusion: Our results show that FD-NIRS is a promising diagnostic tool to detect changes in cervical concentrations of hemoglobin and water. A severe tissue edema, probably due to a hormone-induced inflammatory process, seems to be important for cervical ripening. The reduction in total hemoglobin is likely to be a consequence of the increased water content of the tissue resulting in a dramatic increase of the distance between vessels. We propose this technology to assess the cervical ripening and eventually to predict preterm labor. Lasers Surg. Med. 39:641-646, 2007 Objective: Preterm labor is a common obstetric complication. Clinical evaluation of cervical ripening to predict preterm labor has a substantial inter-and intraobserver variability. We used frequency domain near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of the optical properties (i.e., absorption and scattering of light) in the uterine cervix during druginduced cervical ripening. Methods: Ten volunteers scheduled for abortion were examined. Optical properties of the uterine cervix were measured and physiological parameters were calculated prior to and after induction of cervical ripening using topical misoprostol. Mean relative changes, AE standard error of the mean as well as statistical significance using the t-test were calculated for oxy-and deoxyhemoglobin, total hemoglobin, oxygen-saturation, and water. The wavelength-dependent decrease of scattering (scatter power) was calculated by an exponential fit and tested with the Wilcoxon test.Results: Misoprostol induced a decrease in total hemoglobin of 21 AE 6% (P < 0.05), a decrease in oxyhemoglobin of 22 AE 6% (P < 0.05), a decrease in deoxyhemoglobin of 16 AE 11% and an increase of 36 AE 8%...

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MMP‐2 expression precedes the final ripening process of the bovine cervix

Engelen

Breeveld-Dwarkasing

Taverne

et al. 2008

Molecular Reproduction Devel

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Collagen is denatured in the gradual cervical ripening process during late pregnancy, already before the onset of final cervical ripening at parturition. Matrix Metallo Proteinases (MMPs) might be responsible for this process. To investigate the presence and potential function of MMPs at the different stages of the ripening process, serial cervical biopsies were obtained from 10 cows at Days 185 and 275 of pregnancy (approximately 5 days before calving), at parturition and at 30 days after parturition. The mRNA and protein expression of MMP-1, MMP-2, and MMP-9 and of the tissue inhibitors of MMPs (TIMP)-1 and TIMP-2 were semi-quantitatively determined using RT-PCR, respectively, zymography, Westernblot, and ELISA techniques and the localization of MMP-2 protein and presence of granulocytes by immunohistochemistry and Luna staining. At parturition compared to 185 days pregnancy the MMP-1 protein expression and the numbers of granulocytes were significantly increased by 3 and 26-fold respectively. MMP-2 mRNA and protein expression had already increased 2.5 (P < 0.05) and twofold (P < 0.05) at 5 days before parturition, prior to final ripening. At that time, MMP-2 was present in smooth muscle cells and extra cellular matrix. TIMP-1 mRNA expression was significantly increased at parturition and TIMP-2 mRNA expression peaked at 5 days before parturition. The increased expression of MMP-2 at 5 days before parturition, suggests that in the cow MMP-2 is responsible for collagen denaturation in the last part of gradual cervical ripening, while MMP-1 and MMP-9 are only active during the final cervical ripening process at parturition.

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Matrix metalloproteinase‐8 correlates with the cervical ripening process in humans

Abstract: The results indicate that MMP-8 is involved in the process of cervical ripening, and that MMP-1 and -3 and their inhibitors TIMP-1 and -2 may also play a role in this complicated process.

Cited by 45 publications

References 38 publications

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

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

Frequency domain near‐infrared spectroscopy of the uterine cervix during cervical ripening

MMP‐2 expression precedes the final ripening process of the bovine cervix

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