Abstract
The purpose of this study was to evaluate the expression of matrix metalloproteinase-3 in the cervix during normal pregnancy and in response to prostaglandin E2 administration to determine how matrix metalloproteinase-3 expression correlates with changes in cervical tensile strength. We assessed cervical tensile strength at different time points in the rat gestation and after the administration of prostaglandin E2. Tensile strength was determined by the cervical creep method. Both active and latent forms of matrix metalloproteinase-3 protein were assayed by immunoblotting and densitometry. Matrix metalloproteinase-3 messenger RNA expression was determined with a real-time reverse transcriptase-polymerase chain reaction technique. Cervical tensile strength decreased through the second half of gestation, reaching a nadir by day 21, at 24 to 48 hours before parturition. Prostaglandin E2 that was administered on day 20 of gestation decreased cervical tensile strength in animals that were pretreated with indomethacin. Prostaglandin E2 treatment before day 20 of gestation produced no change in cervical tensile strength. Matrix metalloproteinase-3 messenger RNA and active protein expression paralleled the changes in cervical tensile strength during normal gestation. No change in total matrix metalloproteinase-3 protein expression was detected after prostaglandin E2 treatment. Matrix metalloproteinase-3 expression parallels changes in cervical tensile strength through pregnancy. Prostaglandin E2 induces the activation of matrix metalloproteinase-3 but does not affect matrix metalloproteinase-3 protein expression, which suggests that matrix metalloproteinase-3 gene transcription is not regulated by prostaglandin E2 but that rather there is another mechanism by which change is induced.
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