Cervical ripening is of crucial importance for reproduction in mammals. The cervix, an organ mainly composed of connective tissue, softens during the last third of pregnancy to facilitate effacement and dilatation during delivery of the newborn. Any change in this physiological pattern, resulting either in preterm or delayed cervical ripening, may have significant consequences. The mechanisms controlling cervical ripening during pregnancy are not completely understood. The known uterotonic properties of platelet-activating factor (PAF), a phospholipid- derived autacoid, and our recent functional studies regarding its effect on the uterine cervix indicate a potential key-role for PAF in parturition. The primary objective of our studies is to further define the role of PAF in cervical ripening in pregnant rats and investigate putative pathways involved in this effect. Furthermore, we propose to determine the effect of different PAF-antagonists on the process of cervical ripening.
Our specific aims are to use timed-pregnant Sprague-Dawley rats to 1) determine the mRNA and protein expression of PAF-acetylhydrolase, the enzyme controlling PAF metabolism, in the uterine cervix at different times of gestation using RT-PCR and Western blot; 2) compare the effects of different doses of PAF, PAF antagonists, and vehicle on cervical ripening as evaluated by measurement of cervical resistance and light induced fluorescence; 3) examine the timing of delivery and duration of parturition in animals treated with PAF, PAF antagonist, or vehicle; and 4) estimate the expressions of iNOS and COX2 mRNA and protein in the cervix of animals treated with PAF, PAF antagonist, or vehicle. These studies would lead to a better understanding of the mechanisms responsible for cervical ripening and therefore might improve our ability to control cervical ripening clinically.
|Maul, Holger; Shi, Leili; Marx, Stephen G et al. (2003) Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide-induced, but not antiprogestin-induced, preterm cervical ripening in timed-pregnant rats. Am J Obstet Gynecol 189:963-7|
|Maul, Holger; Shi, Leili; Marx, Stephen G et al. (2002) Local application of platelet-activating factor induces cervical ripening accompanied by infiltration of polymorphonuclear leukocytes in rats. Am J Obstet Gynecol 187:829-33|