title: Cervical remodeling/ripening at term and preterm delivery: the same mechanism initiated by different mediators and different effector cells.
abstract: BACKGROUND
  Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We previously demonstrated that complement activation plays a causative role in cervical remodeling that leads to PTD in mice.
  
  
  RESULTS
  Here we found that complement activation is not required for the physiological process that leads to term delivery in mice. Neither increased C3 cervical deposition nor increased C3a and C5a serum levels were observed at term. In addition, macrophages infiltration was found in PTD in contrast to term delivery were no leukocytes were found. Despite the different role of complement and different cellular effector cells, PTD and term delivery share a common dowsntream pathway characterized by increased metalloproteinases (MMPs) release and increased collagen degradation. However, different sources of MMPs were identified. Macrophages are the source of MMPs in PTD while cervical fibroblasts and columnar epithelial cells synthesize MMPs at term delivery. A dramatic diminution in serum progesterone levels precedes parturition at term but not in PTD, suggesting that progesterone withdrawal initiates cervical remodeling at term. On the other hand, MMPs release in PTD is triggered by C5a.
  
  
  CONCLUSIONS
  In conclusion, preterm and term cervical remodeling occur through the same mechanism but they are initiated by different mediators and effector cells. That complement activation is required for PTD but not for the physiological process that leads to term delivery, suggests that complement is a potential specific biomarker and selective target to prevent PTD and thus avert neonatal mortality and morbidity.
authors.affiliation: Perinatology Research Branch, National Institute of Child Health and Human Development/National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Gonzalez
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Guillermina
authors.initials: G
authors.lastname: Girardi
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000201:enzymology / Q000502:physiology*; D003167:Complement Activation; D005260:Female; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011374:Progesterone; D020782:Matrix Metalloproteinases
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