Smooth Muscle Cells of the Bovine Cervical Stroma may have a Secretory, rather than a Contractile Function during Parturition

Engelen, E. van; Breeveld-Dwarkasing, V.N.A.; Everts, M. E.; Weyden, G. C. van der; Taverne, M.A.M.; Rutten, Victor P.M.G.

doi:10.1111/j.1439-0531.2008.01070.x

Cited by 7 publications

(4 citation statements)

References 59 publications

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“…Moreover, we also found that PGE 2 in intrapartum uterine cervix is also able to be produced or secreted in vascular endothelium, squamous epithelium, glandular epithelium, serosa, mesenchymal cells, and circular and longitudinal smooth muscle. This is in agreement with the observations made by Engelen et al [54] who found that many of the smooth muscle cells distributed over the outer muscular layer and within the stromal layer in the bovine cervix at parturition have a secretory function. In addition, it is possible that the PGE 2 secreted by the caprine uterine cervix has a paracrine and autocrine function in the cervix itself or in ambient tissues and cells.…”

Section: Pge 2 and Its Four Receptorssupporting

confidence: 93%

Immunolocalization of Adipocytes and Prostaglandin E2 and Its Four Receptor Proteins EP1, EP2, EP3, and EP4 in the Caprine Cervix During Spontaneous Term Labor1

Gu¹,

Gao²,

Yuan³

et al. 2012

Biology of Reproduction

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The mechanisms of cervical ripening and dilation in mammals remain obscure. Information is lacking about the localization of prostaglandin E(2) (PGE(2))-producing cells and PGE(2) receptors (EP) in intrapartum cervix and whether cervical dilation at parturition is an active process. To reveal these mechanisms, immunolocalization of EP1-EP4 (official gene symbols PTGER1-PTGER4) and PGE(2)-producing cells in caprine cervix during nonpregnancy, pregnancy, and parturition was assayed by immunohistochemistry (IHC); the mRNA expression levels of PTGS2, PTGER2 (EP2), and PTGER4 (EP4) were determined using quantitative PCR; and the existence of adipocytes in the cervix at various stages was demonstrated with Oil Red O staining and IHC of perilipin A. The results suggested that in intrapartum caprine cervix staining of the PGE(2) was observed in the overall tissues, for example, blood vessels, canal or glandular epithelia, serosa, circular and longitudinal muscles, and stroma in addition to adipocytes; EP2 was detectable in all the tissues other than glandular epithelia; EP4 was strongly expressed in all the tissues other than serosa; EP1 was detected mainly in arterioles and canal or glandular epithelia; and EP3 was poorly expressed only in stroma, canal epithelia, and circular muscles. Little or no expression of EP2, EP3, and EP4 as well as PGE(2) in all cervical tissues was observed during nonpregnancy and pregnancy except for the strong expression of EP1 in canal or glandular epithelia during pregnancy. The mRNA expression levels of PTGS2, PTGER2, and PTGER4 were significantly higher in intrapartum than nonpregnant and midpregnant cervices (P < 0.01). Adipocytes appear only in the intrapartum cervix. These results support the concept that PGE(2) modulates specific functions in various anatomical structures of the caprine cervix at labor and the appearance of adipocytes at labor is likely related to caprine cervical dilation.

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Section: Pge 2 and Its Four Receptorssupporting

confidence: 93%

Immunolocalization of Adipocytes and Prostaglandin E2 and Its Four Receptor Proteins EP1, EP2, EP3, and EP4 in the Caprine Cervix During Spontaneous Term Labor1

Gu¹,

Gao²,

Yuan³

et al. 2012

Biology of Reproduction

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“…One part of each biopsy sample was snap‐frozen in liquid nitrogen, and stored at −80°C until further analysis and the other part was fixed in 4.5% formaldehyde in phosphate‐buffered saline (PBS) for 24 h and embedded in paraffin. These biopsy samples were also used in a previous study (van Engelen et al. 2008a).…”

Section: Methodsmentioning

confidence: 99%

Cervical Ripening and Parturition in Cows are Driven by a Cascade of Pro‐Inflammatory Cytokines

Engelen¹,

Groot²,

Breeveld-Dwarkasing³

et al. 2009

Reprod Domestic Animals

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The final stages of cervical ripening and parturition resemble an inflammatory process. Although the role of cytokines in both spontaneous and experimentally induced parturitions has been described in several small laboratory animals and humans, the involvement of pro-inflammatory and regulatory cytokines in physiologic parturition in cows has not been determined. In this study, the cytokine expression profiles were assessed in bovine cervical tissue at several stages of pregnancy and at parturition. Serial biopsy samples of the cervix were obtained from 10 cows on day 185 and day 275 of pregnancy (which was on average 5.4 days before parturition) and at parturition. Messenger RNA expression levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)alpha were determined using real-time polymerase chain reaction and the number of neutrophils and eosinophils was estimated by Luna and Sirius Red staining. At parturition, IL-8 expression had increased 430-fold (p < 0.001) when compared with that of the day 185 of pregnancy, large numbers of neutrophils had invaded the cervix while eosinophils remained scarce, IL-1beta had increased eightfold (p < 0.05) and IL-6 had not changed significantly. Additionally, IL-10 was increased by 10-fold (p < 0.001) and TNFalpha decreased by 57% (p < 0.05) when compared with that of the day 185 of pregnancy. The large increase in expression of IL-8, enabling the influx of neutrophils, is indicative of its important role in the final stage of cervical ripening and at parturition. As previous studies have shown that neutrophils excrete matrix metalloproteinases (MMP), this might contribute to softening of the cervix. In contrast, the only slightly increased levels of IL-1, steady concentrations of IL-6 and decreased TNFalpha, the potential consequences of increased IL-10 expression, indicate that final cervical of cows in ripening at term parturition is an inflammatory process influenced by regulatory cytokines.

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“…The localization of the brown MMP-2 staining was assessed by light microscopy. Since in the cervical stroma, smooth muscle cells (SMC) are oriented in bundles surrounded by connective tissue which contains fibroblasts (Van Engelen et al, 2008), it was possible to estimate which cells stained positive for MMP-2, and if MMP-2 was present in the ECM.…”

Section: Immuno Histochemistry For Mmp-2mentioning

confidence: 99%

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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Smooth Muscle Cells of the Bovine Cervical Stroma may have a Secretory, rather than a Contractile Function during Parturition

Cited by 7 publications

References 59 publications

Immunolocalization of Adipocytes and Prostaglandin E2 and Its Four Receptor Proteins EP1, EP2, EP3, and EP4 in the Caprine Cervix During Spontaneous Term Labor1

Immunolocalization of Adipocytes and Prostaglandin E2 and Its Four Receptor Proteins EP1, EP2, EP3, and EP4 in the Caprine Cervix During Spontaneous Term Labor1

Cervical Ripening and Parturition in Cows are Driven by a Cascade of Pro‐Inflammatory Cytokines

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

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