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Mol. Hum. Reprod. Advance Access published online on March 2, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gal117
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition

Erik Malmström1, Maria Sennström2, Anna Holmberg1, Helena Frielingsdorf1, Erik Eklund1, Lars Malmström3, Ellen Tufvesson1, Maria F. Gomez1, Gunilla Westergren-Thorsson1, Gunvor Ekman-Ordeberg2 and Anders Malmström1,4

1 Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden 2 Department of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden 3 Department of Biochemistry, University of Washington, Seattle, USA

4 To whom correspondence should be addressed at: Department of Experimental Medical Science, C13, BMC, Lund University, S-221 84 Lund, Sweden. Tel: +46 46 2228574; Fax: +46 46 2223128; E-mail: anders.malmstrom{at}med.lu.se

It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in {alpha}-smooth actin and prolyl-4-hydroxylase and an increase in interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade.

Key Words: Fibroblast/human uterine cervix/interleukins/proteome/remodelling

Submitted on October 7, 2006; resubmitted on December 19, 2006; accepted on December 29, 2006.


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