MMP-2 expression precedes the final ripening process of the bovine cervix.
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.
van Engelen
E
E
Department of Pathobiology, Division of Anatomy and Physiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. erikvanengelen@kliksafe.nl
Breeveld-Dwarkasing
V N A
VN
Taverne
M A M
MA
Everts
M E
ME
van der Weijden
G C
GC
Rutten
V P M G
VP
D000818:Animals; D002417:Cattle; D020070:Cervical Ripening / Q000502:physiology*; D002584:Cervix Uteri / Q000201:enzymology*; D005260:Female; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D036801:Parturition / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics
D011257:Pregnancy Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1