Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events.
OBJECTIVE
The purpose of this study was to assess the structural, biomechanical, and biochemical effects of mifepristone-induced progesterone withdrawal on the rat cervix to identify possible mechanisms by which mifepristone incites cervical ripening.


METHODS
After the administration of mifepristone, cervical tensile strength was determined by the cervical creep method. With polarized light microscopy and transmission electron microscopy, collagen organization and microstructure were quantified. Matrix metalloproteinase expression was assessed by Western Blot and Real-time reverse transcriptase-polymerase chain reaction.


RESULTS
Mifepristone induced a decrease in cervical tensile strength at mid gestation that was associated with a decrease in collagen organization. Additionally, mifepristone led to collagen fragmentation with a significant decrease in fibril length and diameter, although fibril bundling remained unaffected. Matrix metalloproteinase-2 expression increased after the administration of mifepristone.


CONCLUSIONS
Mifepristone-induced cervical ripening is associated with collagen degradation, and the collagenase activity of matrix metalloproteinase-2 may play a role in this process.
Clark
Kelley
K
Department of Obstetrics and Gynecology, University of Vermont, Burlington, VT 05401, USA. kelley.clark@vtmednet.org
Ji
Huiling
H
Feltovich
Helen
H
Janowski
Jessie
J
Carroll
Colleen
C
Chien
Edward K
EK
D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects*; D002584:Cervix Uteri / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D003094:Collagen / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006727:Hormone Antagonists / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D008859:Microscopy, Polarization; D015735:Mifepristone / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000187:drug effects
D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D011374:Progesterone; D003094:Collagen; D020778:Matrix Metalloproteinase 2