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Stephen G . Marx \r \nThe University of Texas Medical Branch at Galveston , April 2005 \r \n \r \nSupervisor : Robert E . Garfield \r \n \r \nThe purpose of these studies is to examine if there is relationship between iNOS and COX -2 in the control of cervical ripening and parturition . Cervices were obtained from estrus and timed pregnant Sprague -Dawley rats (n = 4 -10 per group ) under normal conditions ; or after treating with LPS (100ƒÝg i .p . ) , Onapristone (3mg /rat ) , progesterone (2 .5 mg , twice daily ) , L -NAME (50mg /day ) , or SNP (0 .3mg /rat ) . Collagen changes were measured and visualized with the picrosirius polarization method . Expression of iNOS and COX -2 mRNA was determined using RT -PCR . Immunohistochemistry (IHS ) was performed for localization of the iNOS and COX -2 enzymes (significance : P <0 .05 ) . Picrosirius polarization showed a decrease in the organization and birefringence of the cervical collagen from the non -pregnant state through pregnancy and is supported by changes in the luminosity (P <0 .001 ) . The iNOS and COX -2 enzymes were mainly localized in the cervical muscle with labeling also in the vascular smooth muscle and epithelium . Under normal term pregnant conditions , iNOS mRNA levels decrease as COX -2 mRNA levels increased demonstrating an inverse correlation (Spearman r = -0 .497 ; P = 0 .00295 ) . Onapristone stimulated preterm labor and /or birth causing a parallel increase in iNOS and COX -2 mRNA demonstrating a positive correlation (Spearman r = 0 .456 ; P = 0 .03 ) . Progesterone prolonged pregnancy stimulating a decrease in the iNOS and COX -2 (P=0 .036 ) mRNA . In comparing term to preterm laboring conditions , there is a significant increase in the iNOS mRNA (P=0 .004 ) but not the COX -2 mRNA . LPS enhanced the iNOS mRNA (P <0 .001 ) but had no effect on the COX -2 mRNA . L -NAME had no effect on the COX -2 or iNOS mRNA . SNP decreased the COX -2 and iNOS with the decrease in the iNOS being significant (P=0 .007 ) . In conclusion , under normal term pregnant conditions iNOS and COX -2 play an important role in regulating cervical ripening and parturition but the pathways appear to act independently of one another in regulating iNOS and COX -2 expression at the mRNA level . Under preterm laboring conditions , when NO is up regulated and /or over expressed , there may be an interaction between the NO and PG pathways in the control of cervical ripening and parturition . \r \n \r \n |