Preventing cervical ripening: the primary mechanism by which progestational agents prevent preterm birth?
OBJECTIVE
Recent clinical trials suggest that progestational agents may prevent preterm birth, specifically in women with short cervices. These studies sought to assess novel pathways by which progestational agents (PAs) may modify signal transduction pathways that are involved in cervical ripening.


METHODS
A microarray analysis was performed on pregnant mouse cervix that was exposed to a MPA. Appropriate microarray and cluster analyses were performed. Target genes of interest were investigated in both PA- and inflammation-exposed cervices by quantitative polymerase chain reaction and immunohistochemistry.


RESULTS
Microarray analysis identified both the previously recognized and novel pathways that are involved in cervical ripening. PAs differentially regulate expression of claudin-2, hyaluronan synthase 2, and lipocalin 2. Claudin expression is significantly decreased by inflammation, which is prevented by PAs.


CONCLUSIONS
PAs significantly modulate gene expression in the cervix in the presence and absence of inflammation. The regulation of these pathways, specifically claudin proteins, may be a critical mechanism by which PAs prevent preterm birth, especially in women with premature cervical shortening.
Xu
Hua
H
Center for Research in Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104-6142, USA.
Gonzalez
Juan M
JM
Ofori
Ella
E
Elovitz
Michal A
MA
D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects* / Q000235:genetics; D002584:Cervix Uteri / Q000737:chemistry; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D051379:Mice; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000517:prevention & control*; D011372:Progestins / Q000494:pharmacology*; D040081:Protein Array Analysis
D011372:Progestins; D017258:Medroxyprogesterone Acetate