子宮頸管熟化制御機構からみた早産の予防(<特集>第57回学術講演会シンポジウム : 早産の予防)

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Background The preterm birth remains one of the important factors and causes that may influence the neonatal morbidity and mortality. Recent research has shown the significant roles of the inflammatory cytokine systems as IL-8 and PGE2 receptors (EP1, EP2, EP3, EP4) in the uterine contractions and cervical ripening in the patients with preterm labor. In the present study, we studied the enhancing effects of hyaluronan, potential inducer of IL-8, and EP4 agonist and inhibitory effects of urinary trypsin inhibitor (UTI), IL-8 inhibitor, and EP4 antagonist on cervical maturations in animal models to investigate the future prevention of preterm delivery in clinical practice. Methods The percent tensile strength with perpendicular stretching, the edematous areas in the unselected microscopic fields and type I collagenase activity in the uterine cervical tissues in the non-pregnant rabbits were examined to evaluate the local effects of vaginal suppository including hyaluronan and synthetic EP4 agonist on the uterine cervix. The effects of vaginal suppository including hyaluronan on the changes of the cervix were also examined in the unselected pregnant women with unripe cervix (Bishop score less than 3) at 34 weeks gestation just prior to the onset of labor prospectively. The inhibitory effects of vaginal suppositories including UTI and synthetic EP4 antagonist in cervical ripening were examined in non-pregnant rabbit's model with LPS-induced cervical ripening. The efficacy of the early treatment with UTI suppository for the maintenance of pregnancy periods and cervical ripening were also evaluated in the pregnant women who were diagnosed as preterm labor with regular uterine contractions and cervical shortening before 25 weeks gestation at our care center retrospectively. Results The vaginal suppositories with Hyaluronan and EP4 agonist showed the increased percent tensile strength, enhanced edematous areas and elevated type I activities in cervix in rabbits significantly compared with controls. Hyaluronan suppositories also showed the significant shortening of duration of labor to delivery compared with control. The vaginal suppositories with UTI and EP4 antagonist revealed the significant inhibitory effects in the LPS-induced cervical ripening model in rabbits. The duration of maintenance of pregnancy was significantly extended in the patients in preterm labor treated with UTI vaginal suppository and tocolytic agents compared with that in patients treated with tocolytic agents alone before 25 weeks of gestation. Conclusions The present study demonstrates the enhancement of cervical ripening by Hyaluronan and EP4 agonist and inhibition of it by UTI and EP4 antagonist in animal models. The successful clinical manipulations of cervical ripening by Hyaluronan and UTI suggest the future treatment of preterm labor by the inhibition of cervical maturation by EP4 antagonist.
社団法人日本産科婦人科学会の論文
2005-10-01

子宮頸管熟化制御機構からみた早産の予防(<特集>第57回学術講演会シンポジウム : 早産の予防)

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